Xiaoaiping injection affects the invasionand metastasis of hepatocellular carcinomaby controlling AFP expression

Objective Xiaoaiping (XAP) is a traditional Chinese medicine that is a commonly used as an anticancerdrug in clinical practice owing to its high efficiency and low toxicity. Specifically, XAP can effectively inhibitthe growth of hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is a key HCC diagnostic marker andis closely related to certain malignant cytological behaviors of HCC. However, whether AFP expression andXAP treatment are related to the invasion and metastasis of HCC remains unclear. In the present study, weaimed to evaluate the effects and underlying mechanism of XAP on the invasion and metastasis of HCC..Methods Using a cell scratch assay, Transwell technology, and western blotting we detected the differentinvasion and metastatic abilities of Hep3B cells in XAP treatment and blank control groups. This allowedcomparison of the invasion and metastatic abilities of Hep3B cells with differing levels of AFP expression.AFP mRNA sequencing technology was used to analyze the mechanism of tumor invasion and metastasisassociated with AFP and XAP treatment.Results Cell invasion and metastasis abilities in the XAP group were significantly lower than those in thecontrol group (P < 0.05). Additionally, compared to the control group, the expression of AFP significantlydecreased after XAP treatment (P < 0.05). The ability of Hep3B cells to invade and metastasize waspromoted when AFP expression was up-regulated, whereas it was inhibited when AFP was silenced. XAPinjection and AFP regulate the invasion and metastatic ability of HCC by affecting matrix metalloproteinases(MMPs).Conclusion XAP injection inhibits the invasion and metastatic ability of HCC by influencing the expressionof AFP;additionally, this inhibition of AFP is achieved by affecting MMPs.

miR-374b-5p suppresses RECK expression and promotes gastric cancer cell invasion and metastasis

AIM: To profile expression of microRNAs (miRNAs) in gastric cancer cells and investigate the effect of miR-374b-5p on gastric cancer cell invasion and metastasis.

Tumor microenvironment: driving forces and potential therapeutic targets for breast cancer metastasis

Distant metastasis to specific target organs is responsible for over 90%of breast cancer?related deaths,but the underlying molecular mechanism is unclear.Mounting evidence suggests that the interplay between breast cancer cells and the target organ microenvironment is the key determinant of organ?specific metastasis of this lethal disease.Here,we highlight new findings and concepts concerning the emerging role of the tumor microenvironment in breast cancer metastasis;we also discuss potential therapeutic intervention strategies aimed at targeting compo?nents of the tumor microenvironment.

Suppression of colorectal cancer metastasis by nigericin through inhibition of epithelial-mesenchymal transition

AIM: To evaluate the effect of nigericin on colorectal cancer and to explore its possible mechanism. METHODS: The human colorectal cancer (CRC) cell lines HT29 and SW480 were treated with nigericin or oxaliplatin under the conditions specified. Cell viability assay and invasion and metastasis assay were performed to evaluate the effect of nigericin on CRC cells. Sphereforming assay and soft agar colony-forming assay were implemented to assess the action of nigericin on the cancer stem cell properties of CRC cells undergone epithelial-mesenchymal transition (EMT). RESULTS: Compared with oxaliplatin, nigericin showed more toxicity for the HT29 cell line (IC50, 12.92 ± 0.25 μmol vs 37.68 ± 0.34 μmol). A similar result was also obtained with the SW116 cell line (IC50, 15.86 ± 0.18 μmol vs 41.02 ± 0.23 μmol). A Boyden chamber assay indicated that a significant decrease in the number of HT29 cells migrating through polyvinylidene fluoride membrane was observed in the nigericin-treated group, relative to the vehicle-treated group [11 ± 2 cells per high-power field (HPF) vs 19.33 ± 1.52 cells per HPF, P < 0.05]. Compared to the control group, the numbers of HT29 cells invading through the Matrigel-coated membrane also decreased in the nigericin-treated group (6.66 ± 1.52 cells per HPF vs 14.66 ± 1.52 cells per HPF, P < 0.05). Nigericin also reduced the proportion of CD133+ cells from 83.57% to 63.93%, relative to the control group (P < 0.05). Nigericin decreased the number of spheres relative to the control group (0.14 ± 0.01 vs 0.35 ± 0.01, P < 0.05), while oxaliplatin increased the number of spheres relative to the control group (0.75 ± 0.02 vs 0.35 ± 0.01; P < 0.05). Nigericin also showed a decreased ability to form colonies under anchorage-independent conditions in a standard soft agar assay after 14 d in culture, relative to the control group (1.66 ± 0.57 vs 7 ± 1.15, P < 0.05), whereas the colony numbers were higher in the oxaliplatin group relative to the vehicle-treated controls (14.33 ± 0.57 vs 7 ± 1.15, P < 0.05). We further detected the expression of E-cadherin and vimentin in cells treated with nigericin and oxaliplatin. The results showed that HT29 cells treated with nigericin induced an increase in E-cadherin expression and a decrease in the vimentin expression relative to vehicle controls. In contrast, oxaliplatin downregulated the expression of E-cadherin and upregulated the expression of vimentin in HT29 cells relative to vehicle controls. CONCLUSION: This study demonstrated that nigericin could partly reverse the EMT process during cell invasion and metastasis.

High level of urokinase plasminogen activator contributes to cholangiocarcinoma invasion and metastasis

AIM: To investigate the role of urokinase plasminogen activator (uPA) in cholangiocarcinoma (CCA) invasion and its correlation with clinicopathological parameters. METHODS: uPA expression in CCA tissue was determined by immunohistochemistry. The level of uPA from two CCA cell lines (HuCCA-1 and KKU-M213) and a noncancer immortalized cholangiocyte cell line (H69) was monitored by plasminogen-gelatin zymography and western blotting, whereas that of plasminogen activator inhibitor type 1 (PAI-1) protein and uPA receptor (uPAR)mRNA was monitored by western blotting and quantitative real-time reverse transcriptase polymerase chain reaction, respectively. Two independent methods were employed to suppress uPA function: a synthetic uPA inhibitor (B428) and silencing of uPA gene expression using siRNA. In vitro invasion of the uPA-disrupted cells was assessed by Matrigel-coated Transwell assay. RESULTS: The immunohistochemical study showed that 75.3% (131/174) of CCA tissues expressed uPA. High uPA expression was correlated with lymphatic invasion and metastasis of CCA patients. Plasminogen-gelatin zymography of the conditioned media and cell-surface eluates showed that both CCA cell lines, but not H69, expressed both secreted and membrane-bound forms of uPA. Although the two CCA cell lines, HuCCA-1 and KKU-M213, expressed a relatively high level of uPA and uPAR, the latter exhibited a much lower degree of in vitro invasiveness, correlating with a high expression of PAI-1 in the latter, but not in the former. Suppressing uPA function with a specific uPA inhibitor, B428, or with siRNA against uPA reduced in vitro invasiveness of KKU-M213 cells, demonstrating the requirement for uPA in the invasiveness of CCA cells. Therefore, our in vivo and in vitro studies suggest that uPA is an important requirement for the invasion process of CCA. CONCLUSION: uPA expression correlates with lymphatic invasion and metastasis in vivo and is required for CCA cell invasion in vitro , suggesting its potential as a therapeutic target.

Regarding on the Fractional Mathematical Model of Tumour Invasion and Metastasis

In this paper,we analyze the behaviour of solution for the system exemplifying model of tumour invasion and metastasis by the help of q-homotopy analysis transform method(q-HATM)with the fractional operator.The analyzed model consists of a system of three nonlinear differential equations elucidating the activation and the migratory response of the degradation of the matrix,tumour cells and production of degradative enzymes by the tumour cells.The considered method is graceful amalgamations of q-homotopy analysis technique with Laplace transform(LT),and Caputo–Fabrizio(CF)fractional operator is hired in the present study.By using the fixed point theory,existence and uniqueness are demonstrated.To validate and present the effectiveness of the considered algorithm,we analyzed the considered system in terms of fractional order with time and space.The error analysis of the considered scheme is illustrated.The variations with small change time with respect to achieved results are effectively captured in plots.The obtained results confirm that the considered method is very efficient and highly methodical to analyze the behaviors of the system of fractional order differential equations.

INVESTIGATION OF THE RELATIONSHIP BETWEEN CELL PROLIFERATIVE ACTIVITY AND INVASION, METASTASIS AND PROGNOSIS OF GASTRIC CANCER

To evaluated Bromodeoxyuridine (BrdUrd) /DNA doubleparametric method in detection of gastric carcinoma and to analyze the relationships of cellular BrdUrd labeling indices(LI), G2/M-phase fraction(G2/MPE) and DNA content to the depth of invasion, lymphatic vessel invasion, lymphatic node metastasis, peritoneal dissemination and blood vessel invasion and prognosis. Methods: Fresh tumor samples from 60 cases were examined by BrdUrd/DNA doubleparametric flowcytometry. Propidium iodide(PI) was used as fluorescent probe for total cellular DNA and a monoclonal antibody against BrdUrd incorporated into DNA. Fluorescein-labeled goat anti-mouse antibody was used as second antibody. Results: The values of BrdUrd LI in patients with serosa invasion was significantly higher than those without serosa invasion (P<0.01); there was statistical significance in 5-year survival rate between the two groups (P<0.01). Both BrdUrd LI and G2/MPF values were significantly higher in patients with lymphatic vessel invasion than those without invasion (P<0.01); the patients with lymphatic vascular invasion carried a significantly poor prognosis (P<0.01). Both BrdUrd LI and G2/MPF values were significantly higher in patients with lymphatic node metastasis than those without metastasis (P<0.01), there was a statistical significance in 5 years survival between these 2 groups. The incidence of lymphatic node metastasis was significantly higher in aneuploid carcinoma (P<0.05), and the patients with aneuploid carried a significantly poor prognosis (P<0.05). Patients with peritoneal dissemination had a significantly worse prognosis (P<0.01). G2/MPF values were significantly higher in patients with blood vessel invasion than those without invasion (P<0.01). Conclusion: Cellular BrdUrd LI, G2/MPF and DNA content are related to depth of invasion, lymphatic vessel invasion, peritoneal dissemination, blood vessel invasion and prognosis of gastric carcinoma.

Decreasing Pin1 suppressed the properties of migratory and invasive in colorectal carcinoma SW620 cells

Objective:The aim of our study was to investigate the effect of Pin1 on the expression of MMP-2 and MMP-9 in human colorectal carcinoma SW620 cells. Methods: We constructed a eukaryotic expression vector of RNA interfering (shRNA) for Pin1 gene (pGenesil-1-Pin1), and then observed its expression in SW620 cells by Western blotting. The cells motility were tested by wound healing assay and Boyden chamber assay. The protein levels and activity of MMP-2 and MMP-9 were tested by Western blotting and Gelatin zymography in SW620 cells after transfected with pGenesil-1-PIN1. Results: pGenesil-1-PIN1 was successfully constructed, which was confirmed by sequencing. Silencing the Pin1 by RNAi significantly decreased the cells motility from 96.4±3.9 per field (×10 objective) to 52.7±4.4 per field (P<0.05, Student's t-test) for SW620 cells transfected with pGenesil-1-PIN1 (SW620/p-shRNA) in Boyden chamber assay, and reduced the MMP-2 and MMP-9 expressions and activity in SW620 cells. The protein relative levels of MMP-2 were 0.32±0.04 for SW620/p-shRNA, and 0.76±0.03 for SW620/p-Con; MMP-9 were 0.41±0.09 for SW620/p-shRNA, and 0.94±0.07 for SW620/p-Con (p<0.05). Conclusion: Inhibited Pin1 expression may contribute to the suppression of the invasive and metastatic capacity of colon cancer cells in vitro.

Study on the mechanism of tRNA-ValAAC-5 in promoting the proliferation and migration of hepatocellular carcinoma cells

Objective:To demonstrate the role and mechanism of tRNA-ValAAC-5 expression in hepatocellular carcinoma(HCC)cells.Methods:The expression levels of tRNA-ValAAC-5 in HCC(Hep3B,HuH7,SNU398,Hep3G2)and human hepatocellular carcinoma(THLE2,THLE3)were detected by real-time PCR.HEP3B and Hep3G2 cells were respectively transfected with tRNA-ValAAC-5-inhibitor and tRNA-ValAAC-5-NC as the inhibitor group and the NC group.Then the ability of cell proliferation was detected by CCK-8 assay and the ability of invasion and metastasis was detected by Transwell assay.The protein expression levels of p21,Matrix metalloproteinase 2(MMP2)and Matrix metalloproteinase 9(MMP9)were determined by Western blot.Results:The relative expression of tRNA-ValAAC-5 in Hep3B,HuH7,SNU398 and Hep3G2 cells were significantly higher than THLE2 and THLE3 cells,the differences were statistically significant(P<0.05).After tRNA-ValAAC-5-inhibitor transfection,the expression of tRNA-ValAAC-5 in Hep3B and Hep3G2 cells were reduced than tRNA-ValAAC-NC group.Both of the differences were statistically significant(t=36.52,27.45,P<0.001),which indicated the transfection was successful.The proliferative ability of Hep3B and Hep3G2 cells transfected with tRNA-ValAAC-5-inhibitor after 24,48,72,96 h were inhibited effectively compared with tRNA-ValAAC-5-NC group.All of the differences were statistically significant in Hep3B(t=5.25,8.23,7.33,14.16,P<0.001)and Hep3G2(t=4.25,5.11,9.39,7.59,P<0.001)cells.The number of invasion and metastasis of Hep3B and Hep3G2 cells were reduced in tRNA-ValAAC-5-inhibitor group compared with tRNA-ValAAC-5-NC group,there was significant difference(t=14.01,21.85,P<0.001).The protein expression levels of P21 were lower,MMP2 and MMP9 were higher in tRNA-ValAAC-5-inhibitor group compared with tRNA-ValAAC-5-NC group,the differences were statistically significant in Hep3B(t=8.96,12.80,4.652,P<0.001)cells and Hep3G2(t=15.17,22.36,12.61,P<0.001)cells.Conclusion:tRNA-ValAAC-5 can effectively promote the proliferation,invasion and metastasis of HCC,and its possible mechanism is related to regulating the expression of p21,MMP2 and MMP9.

Blockade of the deubiquitinating enzyme USP48 degrades oncogenic HMGA2 and inhibits colorectal cancer invasion and metastasis

HMGA2,a pivotal transcription factor,functions as a versatile regulator implicated in the progression of diverse aggressive malignancies.In this study,mass spectrometry was employed to identify ubiquitin-specific proteases that potentially interact with HMGA2,and USP48 was identified as a deubiquitinating enzyme of HMGA2.The enforced expression of USP48 significantly increased HMGA2 protein levels by inhibiting its degradation,while the deprivation of USP48 promoted HMGA2 degradation,thereby suppressing tumor invasion and metastasis.We discovered that USP48 undergoes SUMOylation at lysine 258,which enhances its binding affinity to HMGA2.Through subsequent phenotypic screening of small molecules,we identified DUB-IN-2 as a remarkably potent pharmacological inhibitor of USP48.Interestingly,the small-molecule inhibitor targeting USP48 induces destabilization of HMGA2.Clinically,upregulation of USP48 or HMGA2 in cancerous tissues is indicative of poor prognosis for patients with colorectal cancer(CRC).Collectively,our study not only elucidates the regulatory mechanism of DUBs involved in HMGA2 stability and validates USP48 as a potential therapeutic target for CRC,but also identifies DUB-IN-2 as a potent inhibitor of USP48 and a promising candidate for CRC treatment.

Relationship between cell adhesion molecules expression and the biological behavior of gastric carcinoma

AIM: To evaluate the relationship between the expression of cell adhesion molecules (CAMs) and the biological behavior of gastric carcinoma. METHODS: Expression of syndecan-1, E-cadherin and integrin β3 were evaluated by immunohistochemical study in a total of 118 gastric carcinomas and 20 non- tumor gastric mucosas. RESULTS: The expressions of syndecan-1 and E-cadherin were significantly lower in gastric carcinoma compared to non-tumor gastric mucosa, and the low expression rates were positively correlated to the tumor invasion depth, vessel invasion, lymph node metastasis and distant metastasis (P < 0.01 in all cases). However, the expression of integrin β3 was significantly higher in gastric carcinoma compared to non-tumor gastric mucosa, and the high expression rates were positively correlated to the tumor invasion depth, vessel invasion, lymph node metastasis and distant metastasis (P < 0.01 in all cases). In addition, the three protein expressions were correlated to the tumor growth pattern (P < 0.01, P < 0.01, and P < 0.05 respectively), but not correlated to tumor differentiation (P > 0.05, P > 0.05 and P > 0.05 respectively). Positive correlation was observed between the expressions of syndecan-1 and E-cadherin, but they which were negatively correlated to the expression of integrin β3 (P < 0.01 in all cases). Univariate analysis demonstrated that the mean survival time and 5-year survival rate were lower in the cases with low expressions of syndecan-1 and E-cadherin and high expression of integrin β3 (P < 0.01, in all cases). COX multivariate analysis showed that the expression level of syndecan-1 could be an independent prognostic index of gastric carcinoma (P < 0.01), whereas E-cadherin and integrin β3 could not be independent indexes (P > 0.05, P > 0.05 respectively). CONCLUSION: The low expression of syndecan-1 and E-cadherin and the high expression of integrin β3 are significantly correlated with the invasion and metastasis of gastric carcinoma, and they are highly correlated with each other. Therefore they may serve as important prognostic markers of gastric carcinoma.

Reduced expression of P120 catenin in cholangiocarcinoma correlated with tumor clinicopathologic parameters

AIM： To investigate the relationship between the expression of P120 and the clinicopathologic parameters in intrahepatic cholangiocarcinoma （ICC）. METHODS： An immunohistochemical study of E-cadherin and P120 catenin was performed on 42 specimens of ICC with a Dako Envision kit. RESULTS： The expression of E-cadherin and P120 was reduced in 27 cases （64.3%） and 31 cases （73.8%）, respectively. Both E-cadherin and P120 expressions were significantly correlated with the tumor histological grade （χ^2 = 9.333, P = 009 and χ^= 11.71, P = 0.003）, TNM stage （χ^= 8.627, P = 0.035 and χ^= 13.123, P = 0.004）, intrahepatic metastasis （χ^= 7.292, P = 0.007 and χ^= 4.657, P = 0.041, respectively） and patients′ survival （χ^= 6.351, P = 0.002 and χ^= 4.023, P = 0.000, respectively）. In addition, the expression of P120 was in concordance with that of E-cadherin （χ^ = 13.797, P = 0.000）, indicating that the expression of P120 may be dependent on that of E-cadherin. Finally, only P120 expression was found to be an independent prognostic factor in Cox regression model （r = 0.088, P = 0.049）. CONCLUSION： Down-regulated expression of E-cadherin and P120 occurs frequently in ICC and contributes to the progression and development of tumor. Both of them may be valuable biologic markers for predicting tumor invasion, metastasis and patients′ survival, but only P120 is an independent prognostic factor for ICC.

Anti-rheumatic Drug Iguratimod(T-614) Alleviates Cancer-induced Bone Destruction via Down-regulating Interleukin-6 Production in a Nuclear Factor-κB-dependent Manner

Cytokines are believed to be involved in a “vicious circle” of progressive interactions in bone metastasis. Iguratimod is a novel anti-rheumatic drug which is reported to have the capability of anti-cytokines. In this study, a rat model was constructed to investigate the effect of iguratimod on bone metastasis and it was found that iguratimod alleviated cancer-induced bone destruction. To further explore whether an anti-tumor activity of iguratimod contributes to the effect of bone resorption suppression, two human breast cancer cell lines MDA-MB-231 and MCF-7 were studied. The effect of iguratimod on tumor proliferation was detected by CCK-8 assay and flow cytometry. The effects of iguratimod on migration and invasion of cancer cells were determined by wound-healing and Transwell assays. Results showed that high dose（30 μg/m L） iguratimod slightly suppressed the proliferation of cancer cells but failed to inhibit their migration and invasion capacity. Interestingly, iguratimod decreased the transcription level of IL-6 in MDA-MB-231 cells in a concentration-dependent manner. Moreover, iguratimod partially impaired NF-κB signaling by suppressing the phosphorylation of NF-κB p65 subunit. Our findings indicated that iguratimod may alleviate bone destruction by partially decreasing the expression of IL-6 in an NF-κB-dependent manner, while it has little effect on the tumor proliferation and invasion.

STUDIES ON THE GAP JUNCTIONAL INTERCELLULARCOMMUNICATION OF HUMAN NASOPHARYNGEALCARCINOMA CELLS AND THE EFFECT OF RII

Human nasopharyngeal carcinoma(NPC) cell line,CNE-2Z, and its clones(L2, H2, L4) with various invasive and metastatic potentials were examined for their gap junctions(GJ), gap junctional intercellular communication(GJIC) and the concentration of cytosolic free calcium(Ca2+). Only a few intermediate junction(IJ)but no GJ structures were observed under electron microscope(EM). CNE-2Z cells showed marked JGIC,while its variants lacked this function using the scraploading dye-transfer technique(SLDT). There was lower concentration of[Ca2+]. in L2 cells(a variant with high invasive and metastatic Potential) compared to that in H2 and L4 cells(variants with medium and low invasive and metastatic Potentials, respectively). These data suggested that high invasive and metastatic potentials might be correlated with the levcl of[Ca2+]i in NPC cells.The effect of RII(4-hydroxycarbophenyl retinamide) on NPC cells also investigated, After 3-7 d of RII(10-5 M) treatment, there was no change in the number of gap junctions and other kind of intercellular junctions in NPC cells observed under EM. The JGIC of CNE-2Z weaked and then disappeared finally with prolonging of RII treatment. However. there was no influence on its variants. The level of[Ca2+], in NPC cells apparently fell after 6 h of RII treatment, and rose to original level with persisting of RII treatment. Whether the fluctuating of[Ca2+]i level is related to the inhibitory effect of RII treatment on growth and invasion of NPC cells needs to be further studied.

Role of adhesion molecules in cancer and targeted therapy

Adhesion molecules mediate cell-to-cell and cell-to-extracellular matrix interactions and transmit mechanical and chemical signals among them.Various mechanisms deregulate adhesion molecules in cancer,enabling tumor cells to proliferate without restraint,invade through tissue boundaries,escape from immune surveillance,and survive in the tumor microenvironment.Recent studies have revealed that adhesion molecules also drive angiogenesis,reshape metabolism,and are involved in stem cell self-renewal.In this review,we summarize the functions and mechanisms of adhesion molecules in cancer and the tumor microenvironment,as well as the therapeutic strategies targeting adhesion molecules.These studies have implications for furthering our understanding of adhesion molecules in cancer and providing a paradigm for exploring novel therapeutic approaches.

Association of E-cadherin and β-catenin with metastasis in nasopharyngeal carcinoma

Background This study was designed to detect methylation of E-cadherin gene promoter and gene mutation of β-catenin in exon 3 and their expression of protein and mRNA in primary tumor and lymph node metastatic tumor of nasopharyngeal carcinoma (NPC), and investigate the mechanism of invasion and metastasis of neoplastic cells in NPC Methods Fourty-two fresh biopsy samples were taken from untreated NPC patients at the Affiliated Hospital of Sun Yat-sen Medical College, Sun Yat-sen University, Guangzhou, China during the period of 1999-2002 Among them 21 were taken from primary tumors and the other 21 from lymph node metastatic tumors The gene promoter methylation of E-cadherin was detected by methylation-specific PCR (MSP) The mutation in exon 3 of β-catenin was detected by direct sequencing analysis RT-PCR, Western blot and immunohistochemical staining were used to detect the mRNA and protein expression patterns in both primary and metastatic tumors of NPC Results Down-regulated expression of E-cadherin in metastatic tumor was compared with that in primary tumor Reduced expression of E-cadherin was found to be correlated with lymph node metastatic tumor of NPC ( P =0 004); but there was no obvious correlation between primary and metastatic tumors in the expression of β-catenin ( P =0 698) The mRNA expression level of E-cadherin in metastatic tumors decreased significantly compared with that in primary tumors However, little change was observed in the mRNA level of β-catenin in different tumor tissues Only 4 samples (19 1%) displayed gene promoter methylation of E-cadherin in primary tumor and 10 samples (47 6%) showed methylated form of E-cadherin The gene promoter methylation of E-cadherin was more common in metastatic tumor than in primary tumor of NPC ( P =0 024) Only 2 (4 76%) of the 42 samples showed mutations in exon 3 of β-catenin at 41 (T41A, ACCGCC) and codon 47 (S47T, AGTACT) The cytoplasmic and nuclear expression of β-catenin in tumor was not found in any samples of NPC Conclusions The results suggest that the downregulation of E-cadherin results from the gene promoter aberrant methylation of E-cadherin and that the methylation of E-cadherin plays an important role in invasion and metastasis of tumor cells in NPC However, β-catenin mutation is an infrequent event in NPC, and β-catenin is not a critical factor influencing the invasion and metastasis of tumor cells in NPC

Role of tissue factor in hepatocellular carcinoma genesis, invasion and metastasis

Background Numerous studies indicate that tissue factor （TF）, namely tissue thromboplastin, has a close relationship with malignant tumor genesis and progress. It contributes to blood coagulation as well as the regulation of cellular differentiation, the formation of blood vessels, and also tumor recurrence and metastasis. The present study aimed to detect TF expression in hepatocellular carcinoma （HCC） patients and to elucidate its association with prognosis and clinical features of the disease. Methods The plasma TF levels of 50 HCC patients and 30 controls were assayed by ELISA. The expressions of TF mRNA and protein in HCC tissues, adjacent tissues and normal tissues were detected by reverse transcription- polymerase chain reaction （RT-PCR） and Western blotting. The acquired data were analyzed with related clinic-pathological documents. The patients were followed up for five years, and the relationship between TF and prognosis was analyzed. Results The plasma TF levels were significantly increased in HCC compared to the controls （P 〈0.05）, presenting a close relationship with differentiation level, tumor size and hepatocirrhosis occurrence （P 〈0.05）. There were remarkably higher values in cases of lymphatic metastasis, extrahepatic metastasis and portal tumor thrombus （PTT） （P 〈0.05） compared to non-metastasis or non-tumor thrombus, but no significant difference with different focus number or envelope （P 〉0.05）. The positive rates and the relative expression of TF mRNA in HCC tissue were 63.0% （17/27） and 0.567±0.268, respectively, significantly higher than that in adjacent tissues or normal tissues （P 〈0.05）. In the patients with positive results, the relative expression intensity varied significantly with different tumor size and index of local invasion and metastasis （P 〈0.05）. The positive rates and the relative expression intensities of TF protein in HCC tissue were 74.1% （20/27） and 4.093±1.256, respectively, significantly higher than those in adjacent tissue or normal tissue （P 〈0.05）. In the patients with positive results, the relative expression intensity showed significant difference in different tumor size, differentiation level, and index of local invasion and metastasis （P 〈0.05）. Conclusions The TF levels were significantly higher in plasma and tissues of HCC patients, presenting a close relationship with the index of invasion and metastasis. It indicated that TF might be related to differentiation and metastasis of HCC.

Positive association of RhoC gene overexpression with tumour invasion and lymphatic metastasis in gastric carcinoma

Worldwide estimates establish gastric carcinoma as the second most frequent cause of cancer deaths. Tumour invasion and metastasis is the biggest impediment to gastric carcinoma cure. Active migration of tumour cells is now considered as the pivotal step in cancer invasion and metastasis. RhoC is a member of the Ras-superfamily of small guanosine triphosphatases that can regulate many cellular functions, especially cytoskeletal organization and cell locomotion. Overexpressing RhoC in vitro in the poorly metastatic cell line from human melanoma may induce a highly metastatic phenotype.~1 The recent development of laser capture microdissection (LCM) affords the opportunity to further evaluate the role RhoC plays in the invasion and metastasis of gastric carcinoma cells in their native tissue environment.

Adverse effects of chemoradiotherapy on invasion and metastasis of tumor cells

The phenomenon of enhanced invasion and metastasis of residual tumor cells has been observed in an increasing number of patients receiving chemoradiotherapy recently,and tumor metastasis will undoubtedly limit patient prognosis.However,the key mechanism by which chemoradiotherapy affects the invasion and metastasis of tumor cells remains unclear.Studies have shown that chemoradiotherapy may directly act on tumor cells and alter the tumor microenvironment,or induce cell apoptosis and autophagy to promote tumor cell survival and metastasis.In this review,we summarize the potential mechanisms by which chemoradiotherapy may affect the biological behavior of tumor cells and open up new avenues for reducing tumor recurrence and metastasis after treatment.These insights will improve the efficacy of chemoradiotherapy.

Lycorine inhibits breast cancer growth and metastasis via inducing apoptosis and blocking Src/FAK-involved pathway

Breast cancer is the most commonly diagnosed cancer type worldwide among women and more than 90% of patients die from tumor metastasis. Lycorine, a natural alkaloid, has been widely reported possessing potential efficacy against cancer proliferation and metastasis. In our study, the anti-tumor potency on breast cancer was evaluated in vitro and in vivo for the first time. Our results indicated that lycorine inhibited breast cancer cells growth, migration and invasion as well as induced their apoptosis.In in vivo study, lycorine not only suppressed breast tumor growth in xenograft models and inhibited breast tumor metastasis in MDA-MB-231 tail vein model. More importantly, we found lycorine had less toxicity than first-line chemotherapy drug paclitaxel at the same effective dose in vivo. Furthermore, on mechanism, lycorine inhibited tumor cell migration and invasion via blocking the Src/FAK(focal adhesion kinase)-involved pathway. In conclusion, our study implied lycorine was a potential candidate for the treatment of breast cancer by inhibition of tumor growth and metastasis.