SENP3 Promotes Mantle Cell Lymphoma Development through Regulating Wnt10a Expression

Objective SUMO-specific protease 3(SENP3),a member of the SUMO-specific protease family,reverses the SUMOylation of SUMO-2/3 conjugates.Dysregulation of SENP3 has been proven to be involved in the development of various tumors.However,its role in mantle cell lymphoma(MCL),a highly aggressive lymphoma,remains unclear.This study was aimed to elucidate the effect of SENP3 in MCL.Methods The expression of SENP3 in MCL cells and tissue samples was detected by RT-qPCR,Western blotting or immunohistochemistry.MCL cells with stable SENP3 knockdown were constructed using short hairpin RNAs.Cell proliferation was assessed by CCK-8 assay,and cell apoptosis was determined by flow cytometry.mRNA sequencing(mRNA-seq)was used to investigate the underlying mechanism of SENP3 knockdown on MCL development.A xenograft nude mouse model was established to evaluate the effect of SENP3 on MCL growth in vivo.Results SENP3 was upregulated in MCL patient samples and cells.Knockdown of SENP3 in MCL cells inhibited cell proliferation and promoted cell apoptosis.Meanwhile,the canonical Wnt signaling pathway and the expression of Wnt10a were suppressed after SENP3 knockdown.Furthermore,the growth of MCL cells in vivo was significantly inhibited after SENP3 knockdown in a xenograft nude mouse model.Conclusion SENP3 participants in the development of MCL and may serve as a therapeutic target for MCL.

Synchronous rectal adenocarcinoma and intestinal mantle cell lymphoma:A case report

BACKGROUND Mantle cell lymphoma(MCL)of the gastrointestinal tract is a rare malignancy,accounting for about 0.2%of malignant colorectal tumors.MCL synchronous with rectal adenocarcinoma is extremely rare.We know of only a few cases reported in the literature.We describe the case of a patient with synchronous rectal adenocarcinoma and intestinal MCL.CASE SUMMARY A 63-year-old man was admitted to our hospital due to abdominal pain and hematochezia over the past month.The patient was diagnosed with middle rectal cancer cT2N0M0 and underwent surgery.However,we found a large tumor in the small intestine during surgery.The patient underwent total mesorectal excision for rectal cancer and resectioning of the ileal segment containing the large mass.Pathology and immunohistochemistry revealed the presence of both rectal adenocarcinoma and pathognomonic MCL stage IIE presenting as multiple lymphomatous polyposis.The patient subsequently underwent RDHAP/RCHOP chemotherapy and was maintained with rituximab.A Positron Emission Tomography and Computed Tomography(PET/CT)scan showed that the disease responded well to treatment without tumor-increased metabolism in the gastrointestinal tract.CONCLUSION Synchronous rectal adenocarcinoma and intestinal MCL presenting as multiple lymphomatous polyposis are extremely rare.MCL is often discovered fortuitously when rectal cancer is diagnosed.The coexistence of these tumors poses treatment challenges.

Endoscopic features and prognoses of mantle cell lymphoma with gastrointestinal involvement

AIM: To evaluate the endoscopic manifestations and prognoses of gastrointestinal (GI) mantle cell lymphoma (MCL). METHODS: A database search at the Department of Pathology of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences revealed 57 MCL patients with GI involvement. Clinical records were available for 35 of the 57 patients from 21 institutions, and those 35 patients were enrolled in this study. We summarized the gross types of endoscopic features, event-free survival (EFS), and overall survival (OS) of those patients.RESULTS: Of the 35 patients, GI involvement in the esophagus, stomach, and duodenum was found in 2 (5.7%), 26 (74.3%), and 12 (34.3%) patients, respectively. Twenty-one of the 35 patients underwent colonoscopy; among them, GI involvement in the ileum, cecum, colon, and rectum was found in 10 (47.6%), 3 (14.3%), 12 (57.1%), and 10 (47.6%), respectively. Various lesions, such as superficial, protruded, fold thickening, or ulcerative, were found in the stomach, whereas multiple lymphomatous polyposis (MLP) was dominant from the duodenum to the rectum. Twelve patients were treated with a hyper-CVAD/MA regimen, and they had better OS (3-year rate, 88.3% vs 46.4%, P < 0.01) and better EFS (3-year rate, 66.7% vs 33.8%, P < 0.05) than the remaining 23 patients who were not treated with this regimen. CONCLUSION: MLP was a representative form of intestinal involvement, whereas a variety of lesions were found in the stomach. The hyper-CVAD/MA regimen may improve survival in these patients.

Single-cell RNA-seq reveals the immune escape and drug resistance mechanisms of mantle cell lymphoma

Objective:Mantle cell lymphoma(MCL)is a rare subtype of non-Hodgkin lymphoma(NHL)with high heterogeneity and a high recurrence rate.How heterogenous cell populations contribute to relapse remains to be elucidated.Methods:We performed single cell RNA sequencing(scRNA-seq)on approximately 4,000 bone marrow cells sampled from one patient with multidrug resistant MCL.We identified 10 subpopulations comprising 4 malignant B cell subtypes,3 T cell subtypes,2 dendritic cell subtypes and 1 natural killer(NK)cell subtype.Subsequently,we identified cell markers,including a series of genes associated with immune escape and drug resistance.In addition,we explored the roles of these genes in the mechanism of immune escape and drug resistance,and we verified the expression imbalance and clinical prognostic potential by using GEO datasets including 211 MCL samples.Results:The major immune escape mechanisms of MCL included anti-perforin activity,decreased immunogenicity and direct inhibition of apoptosis and cell killing,as mediated by type I and II B cells.The drug resistance mechanisms of different cell clusters included drug metabolism,DNA damage repair,apoptosis and survival promotion.Type III B cells closely communicate with other cells.The key genes involved in the resistance mechanisms showed dysregulated expression and may have significant clinical prognostic value.Conclusion:This study investigated potential immune escape and drug resistance mechanisms in MCL.The results may guide individualized treatment and promote the development of therapeutic drugs.

Targeting EZH1/2 induces cell cycle arrest and inhibits cell proliferation through reactivation of p57CDKN1C and TP53INP1 in mantle cell lymphoma

Objective: To explore the effect of dysregulation of epigenetic regulator EZH1 and EZH2 on the proliferation in MCL and the underlying mechanisms.Methods: In this study, we elucidated the role of EZH1 and EZH2 overexpression by immunohistochemistry and correlated them to clinical outcome in 41 MCL patients.Quantitative real-time PCR and Western blot were applied to confirm the level of EZH1 and EZH2 in well-characterized MCL cell lines which were compared to those of na?ve B cells.Then we manipulated the expression of EZH1 and EZH2 in MCL cells using CRISPR/Cas9 system to directly investigate their functional roles in MCL.We also evaluated the effect of two small molecule selective inhibitors, EPZ005687 and UNC1999, on MCL cell proliferation, cell cycle distribution and apoptosis in vitro.Finally, we performed RNA-sequencing(RNA-Seq) and Chromatin immunoprecipitation(ChIP) assay to further gain insight into the underlying molecular mechanisms.Results: We found that EZH2 protein is overexpressed in approximately half of this cohort of MCL cases.More importantly, the overexpression of EZH2 is associated with poor OS in the patients.Nevertheless, simple EZH2 depletion in vitro has little impact on the viability of MCL cells, predominantly because of the consequent up-regulation of EZH1.Consistently, UNC1999, a dual EZH1/2 inhibitor, unlike the EZH2 selective inhibitor EPZ005687, exerts a potent inhibitory effect on MCL cells.Furthermore, we discover CDKN1C and TP53 INP1 as the two important cell cycle regulators, the expression of which are repressed by EZH1/2 mediated epigenetic regulation and are restored by EZH1/2 dual inhibition.Conclusions: Our study suggests that EZH2 participates in the pathogenesis of MCL which may serve as a potential biomarker for prognosis prediction.The dual inhibition of EZH1/2 is a promising therapeutic strategy for MCL.

The clinical features, therapeutic responses, and prognosis of the patients with mantle cell lymphoma

Mantle cell lymphoma(MCL), a special type of non-Hodgkin's lymphoma, is incurable through conventional treatment. This study aimed to analyze the clinical features, therapeutic responses, and prognosis of patients with MCL. Clinical data of 30 patients with MCL treated in our hospital between April 2006 and July 2011 were analyzed. Eighteen patients were treated with CHOP plus rituximab (R-CHOP) regimen, 12 underwent conventional chemotherapy. The median age of the 30 patients was 58 years, 23 were men, all patients had Cyclin D1 overexpression, 29 (96.7%) had advanced disease, 11 (36.7%) had bone marrow involvement, 9 (30.0%) had gastrointestinal involvement, and 15 (50.0%) had splenomegaly. The complete response(CR) rate and overall response rate(ORR) were significantly higher in patients undergoing R-CHOP immunochemotherapy than in those undergoing conventional chemotherapy (38.9% vs. 16.7%, P = 0.187; 72.2% vs. 41.4%, P = 0.098). The difference of 2-year overall survival rate between the two groups was not significant (P = 0.807) due to the short follow-up time. The 2-year progression-free survival (PFS) rate was higher in R-CHOP group than in conventional chemotherapy group (53% vs. 25%, P = 0.083), and was higher in patients with a lower mantle cell lymphoma international prognostic index (MIPI) (51% for MIPI 0-3, 33% for MIPI 4-5, and 0% for MIPI 6-11, P = 0.059). Most patients with MCL were elderly; in an advanced stage; showed a male predominance; and usually had bone marrow involvement, gastrointestinal involvement, or splenomegaly. R-CHOP regimen could improve the CR rate and ORR of MCL patients. MIPI can be a new prognostic index for predicting the prognosis of advanced MCL.

Clinicopathologic features of 112 cases with mantle cell lymphoma

Objective： This study aims to explore the clinicopathologic features of 112 patients with mantle cell lymphoma （MCL）. Methods： Data from 112 MCL cases were collected, and immunohistochemical assay was conducted. Fluorescence in situ hybridization （FISH） detected a break in the CCND 1 gene. The t-test was used in the statistical analysis. Results： All tumor cells in the 112 cases expressed B cell-related antigen, including 1 blastoid subtype and 1 polymorphic subtype. Among all cases, 106 expressed CD5 and 104 expressed cyclin D1. A break in the CCND1 gene was not found in 3 cases with CDS-MCL. IgH/CCND 1 polyploid was observed in 2 classic cases. Conclusion： MCL is a type of special immunophenotypic B-cell lymphoma, The prognoses ofblastoid and polymorphic subtypes are poor. Special subtypes should be classified during diagnosis.

Coexistence of hepatoma with mantle cell lymphoma in a hepatitis B carrier

The coexistence of hepatocellular carcinoma(HCC) and non-Hodgkin's lymphoma(NHL) in the liver is rare. Reports show that these patients have cirrhotic livers or hepatitis virus infections before they develop HCC and NHL. We present a patient with hepatitis B virus infection who was transferred to our hospital with a newly detected liver mass; abdominal computed tomography examination showed one hypodense mass of 7 cm in diameter and multiple mesenteric and mediastinal lymph nodes. A liver tumor biopsy showed a hepatoma, and the pathologic findings from an inguinal lymph node excision showed mantle cell lymphoma. An immunohistochemical stain confirmed that the atypical lymphoid cells within the HCC were positive for the CD20, CD5 and cyclin D1 antigens. Taking these findings into account, the hepatic tumor was determined to be a HCC infiltrated by mantle cell lymphoma.

^(18)F-FDG PET/CT imaging for a gastrointestinal mantle cell lymphoma with multiple lymphomatous polyposis

Multiple lymphomatous polyposis(MLP)is an uncommon type of gastrointestinal lymphoma characterized by the presence of multiple polyps along the gastrointestinal tract.Most of this entity is in fact considered the counterpart of gastrointestinal tract involvement for mantle cell lymphoma(MCL).To our knowledge,there have been no reports on[fluorine-18]-fluorodeoxy-glucose(18F-FDG)-positron emission tomography(PET)/computed tomography(CT)imaging for gastrointestinal MCL with MLP.We present the results of 18F-FDG PET/CT imaging in a patient with gastrointestinal tract involvement of MCL showing continuous MLP from the stomach to the rectum and intestinal intussusception.FDG-PET/CT findings were false negative in typical MLP spreading widely over the gastrointestinal tract,but uptake was noted in large lesions with deep infiltration considered atypical as MLP.On FDG-PET/CT imaging,the Ki-67proliferative index,which is a cell proliferation marker,showed neither correlation with the presence of uptake nor the maximum standardized uptake value.

Mantle Cell Lymphoma in a Lacrimal Gland in a Female and a Review of the Literature

Purpose:To report a rare case of Mantle cell lymphoma in lacrimal gland and review of the literature Case report:.We report a case of a 59-year-old female who presented with an upper eyelid mass in the right eye for 3months, without pain and irrigation. A computerized tomography(CT) scan showed a mass in the bilateral lacrimal gland region, more significant in right eye. The patient underwent a lacrimal gland mass excision surgery and diagnosis of mantle cell lymphoma by histopathology..Immunochemistry for CD20, CD79 a, CD5, and Cyclin D1 was positive. She was recommended to the Shantou cancer hospital for chemotherapy.Conclusion:.Mantle cell lymphoma is a rare type of malignant lymphoma,.over expressing CD5 and cyclin D1 antigens,which distinguishes it from other B cell lymphomas.

Synergistic suppression of the PI3K inhibitor CAL-101 with bortezomib on mantle cell lymphoma growth

Objective: To investigate the effects of CAL-101, particularly when combined with bortezomib(BTZ) on mantle cell lymphoma(MCL) cells, and to explore its relative mechanisms.Methods: MTT assay was applied to detect the inhibitory effects of different concentrations of CAL-101. MCL cells were divided into four groups: control group, CAL-101 group, BTZ group, and CAL-101/BTZ group. The expression of PI3K-p110σ, AKT, ERK, p-AKT and p-ERK were detected by Western blot. The apoptosis rates of CAL-101 group, BTZ group, and combination group were detected by flow cytometry. The location changes of nuclear factor kappa-B(NF-κB) of 4 groups was investigated by NF-κB Kit exploring. Western blot was applied to detect the levels of caspase-3 and the phosphorylation of AKT in different groups. Results: CAL-101 dose- and time-dependently induced reduction in MCL cell viability. CAL-101 combined with BTZ enhanced the reduction in cell viability and apoptosis. Western blot analysis showed that CAL-101 significantly blocked the PI3K/AKT and ERK signaling pathway in MCL cells. The combination therapy contributed to the inactivation of NF-κB and AKT in MCL cell lines. However, cleaved caspase-3 was up-regulated after combined treatment. Conclusion: Our study showed that PI3K/p110σ is a novel therapeutic target in MCL, and the underlying mechanism could be the blocking of the PI3K/AKT and ERK signaling pathways. These findings provided a basis for clinical evaluation of CAL-101 and a rationale for its application in combination therapy, particularly with BTZ.

Correlation of PI3K/Akt signaling pathway with cell apoptosis and invasion in mantle cell lymphoma

Objective: To study the correlation of PI3K/Akt signaling pathway with cell apoptosis and invasion in mantle cell lymphoma. Methods: A total of 38 patients who were diagnosed with mantle cell lymphoma in Xijing Hospital Affiliated to the Fourth Military Medical University between June 2014 and March 2017 were selected as the MCL group of the research, 55 patients who were diagnosed with reactive lymphoid hyperplasia in Xijing Hospital Affiliated to the Fourth Military Medical University during the same period were selected as the control group of the research, and lymph node tissue was collected to detect the protein expression of p-PI3K and p-AKT as well as the mRNA expression of apoptosis genes and invasion genes. Results: p-PI3K and p-AKT protein expression as well as SOX11, cyclinD1, TNFAIP3, XIAP, PCNA, MMP2, MMP7, MMP9 and VEGF mRNA expression in lymph node of MCL group were significantly higher than those of control group while TNFAIP3 mRNA expression was significantly lower than that of control group;SOX11, cyclinD1, XIAP, PCNA, MMP2, MMP7, MMP9 and VEGF mRNA expression in MCL lymph node with high p-PI3K expression were significantly higher than those in MCL lymph node with low p-PI3K expression while TNFAIP3 mRNA expression was significantly lower than that in MCL lymph node with low p-PI3K expression. Conclusion: The activation of PI3K/Akt signaling pathway in mantle cell lymphoma is closely related to the tumor cell apoptosis disorder and invasion enhancement.

Potential effects of CRM1 inhibition in mantle cell lymphoma

Mantle cell lymphoma （MCL） is an aggressive histotype of B-cell non-Hodgkin lymphoma. The disease has no known cure, which prompts the urgent need for novel therapeutic agents. Chromosomal region maintenance 1 （CRM1） may play a role in human neoplasia and serve as a novel target of cancer treatment. This study summarizes MCL pathogenesis and determines the involvement of CRM1 in the regulation of several vital signaling pathways contributing to MCL pathogenesis, including the pathways of cell cycle progression, DNA damage response, phosphoinositide kinase-3, nuclear factor-kB activation, and chromosomal stability. A preclinical study is also presented to compare the CRNI1 status in MCL cell lines and primary MCL cells with normal B cells, as well as the therapeutic efficiency of CRM1 inhibition in MCL in vitro and in vivo, which make these agents potential targets of novel MCL treatments.

EHMT2 (G9a) activation in mantle cell lymphoma and its associated DNA methylation and gene expression

Objective:The function of euchromatic histone-lysine N-methyltransferase 2(EHMT2)has been studied in several cancers;however,little is known about its role in mantle cell lymphoma(MCL).Thus,this study aimed to characterize the significance and function of EHMT2 in MCL.Methods:EHMT2 expression in MCL and reactive hyperplasia(RH)were investigated by immunohistochemistry.Genome-wide analysis of DNA methylation was performed on EHMT2+MCL samples.The function of EHMT2 was determined by CCK&flow cytometry,and western blot assays.Gene expression profile analysis was performed before and after EHMT2 knockdown to search for EHMT2-regulated genes.Co-immunoprecipitation(Co-IP)experiments were conducted to identify the proteins interacting with EHMT2.Results:EHMT2 was expressed in 68.57%(24/35)of MCLs but not in any RHs.Genome-wide analysis of DNA methylation on EHMT2+MCLs revealed that multiple members of the HOX,FOX,PAX,SOX,and CDX families were hypermethylated or hypomethylated in EHMT2+MCLs.BIX0I294,a EHMT2 inhibitor,inhibited MCL cell growth and stalled cells in the G1 phase.Additionally,BIX01294 downregulated the expressions of cell cycle proteins,cyclin DI,CDK4,and P21,but upregulated the expressions of apoptosis-related proteins,Bax and caspase-3.Co-IP experiments revealed that EHMT2 interacted with UHRF1,HDAC1,and HDAC2 but not with HDCA3.After EHMT2 knockdown,multiple genes were regulated,including CD5 and CCND1,mostly enriched in the Tec kinase signaling pathway.In addition,several genes(e.g.,MARCH 1,CCDC50,HIP1,and WNT3)were aberrantly methylated in EHMT2+MCLs.Conclusions:For the first time,we determined the significance of EHMT2 in MCL and identified potential EHMT2-regulated genes.

Primary cutaneous mantle cell lymphoma:Report of a rare case

BACKGROUND We describe the case of a 74-year-old man diagnosed with primary cutaneous mantle cell lymphoma(MCL),an extremely rare and controversial condition that is not included in the World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas.CASE SUMMARY The patient presented diffuse cutaneous erythematous plaques and nodules throughout the body.Skin lesions were biopsied and histopathological examination showed diffuse monomorphic lymphocyte infiltration in the dermal and subcutaneous layers,sparing the epidermis.Immunohistochemical staining revealed CD20,cyclin-D1,CD5,and SOX-11 expression.Fluorescence in situ hybridization showed CCND1/IGH gene rearrangement.Correct diagnosis of primary cutaneous MCL requires ensuring that no other parts are involved;these cases require close follow-up to monitor their possible progression to systemic disease and for treating relapsed cutaneous disease.In this case,positron emission tomography scanning and clinical staging revealed no systemic involvement,and follow-up examination at 20 mo after diagnosis showed no evidence of systemic disease.The prognosis of primary cutaneous MCL is relatively good.Our patient received six cycles of chemotherapy,and the cutaneous manifestations presented almost complete remission.CONCLUSION Primary cutaneous MCL is rare,and its prognosis is relatively favorable.However,correct diagnosis is a prerequisite for proper treatment.

Mantle cell lymphoma with endobronchial involvement:A case report

BACKGROUND Mantle cell lymphoma(MCL)is a subtype of Non-Hodgkin’s lymphoma(NHL).MCL frequently affects extranodal sites while endobronchial involvement is uncommon.Only 5 cases of MCL with endobronchial involvement have been previously reported.CASE SUMMARY A 56-year-old male patient arrived at the hospital complaining of a dry cough.A mass in the right upper lobe of the lung was revealed in Chest computed tomography(CT).Right lung hilar and mediastinal lymphadenopathies were also found by CT scan.The patient was diagnosed with central-type lung cancer with multiple lymph node metastases after positron emission tomography(PET)CT scan examination.The fiber optic bronchoscope examination revealed diffuse neoplasm infiltration in the inlet of the right up lobar bronchus.The patient was finally diagnosed with MCL based on the bronchoscopy and mediastinoscopy biopsy results.CONCLUSION MCL could masquerade as central type lung cancer.An endobronchial biopsy examination is necessary for the early diagnosis of MCL.

Biased Immunoglobulin Genes Rearrangement in Mantle Cell Lymphoma： Hints to Identify the Normal B-cell Counterpart

Mantle cell lymphoma （MCL） is an aggressive nonHodgkin＇s lymphoma, originating from naive B-cells. The blastoid MCL tumors often show complex cytogenetic aberrations. In this review, we summarized the data available on immunoglobulin heavy-chain （IgH） genes rearrangement for their importance in suggesting the MCL normal counterpart B-cell. Some new data suggesting an antigen selection process were also presented in this review.

Meta-Analysis of the Efficacy and Adverse Reactions of Ibrutinib in the Treatment of Refractory/Relapsed Mantle Cell Lymphoma

Objective: Therapeutic results of relapsed/refractory mantle cell lymphoma (R/R MCL) are very disappointing at present, and there is no standard effective treatment regimen. Ibrutinib has been proved to be effective for R/R MCL, however, the sample size of these individual clinical studies was relatively small. Hence, current clinical experience in its usage is still limited. It is necessary to systematically analyze the efficacy and adverse reactions of ibrutinib in the treatment of R/R MCL. Methods: The PubMed, Cochrane Library, and Embase databases were searched using English search terms, mantle cell lymphoma, MCL, and ibrutinib;the VIP, Wanfang, and China National Knowledge Infrastructure (CNKI) databases were searched using the Chinese search terms, ibrutinib and mantle cell lymphoma. The extracted data were subjected to meta-analysis using R software to deduce the effective rate and occurrence rate of serious adverse reactions. Results: A total of 12 cohort studies were included in this analysis. The results demonstrated that ibrutinib could be an efficient therapy regimen for R/R MCL patients and the effect of combination therapy was better than that of single-drug therapy. During the treatment with ibrutinib, the adverse reactions mainly included hematological toxicity, infection, atrial fibrillation, and bleeding. Discussion: Our analysis showed ibrutinib is an optimal second-line treatment for R/R MCL, and the combination therapy is more effective than monotherapy as it was well-tolerated by the patients. Therefore, the combination of other drugs for R/R MCL should be considered for patients with poor efficacy of ibrutinib alone or relapse after treatment.

Matrigel modulates a stem cell phenotype and promotes tumor formation in a mantle cell lymphoma cell line

Tumors may be maintained by subpopulations of cells possessing stem cell-like properties. We evaluated the stem cell-like and tumor-forming properties of side population (SP) and CD133+/ CD44+ cells in Granta 519, a human mantle cell lymphoma cell line. The in-vitro Cobblestone Area Forming Cell (CAFC) assay, designed to detect stem and progenitor cells, revealed that SP cells contained the greatest proportion of stem cell-like cells. The addition of Matrigel to CAFC assays of SP and non-SP cells both increased their respective stem cell frequencies in comparison to those cultures without Matrigel, and additionally resulted in observed stem cell frequencies which were the same between SP and non-SP cells. Contrary, Matrigel decreased the stem cell frequencies of CD133+/CD44+ or CD133-/CD44- cells. In-vivo assays revealed tumor formation from Matrigel-mixed SP and non-SP cells, and in one instance, occurred with as few as one Matrigel-mixed SP cell. Vehicle-mixed injections of SP and non-SP tumor cells resulted in tumor formation from SP cells only. Tumor formation did not occur from Matrigel nor hyaluronan (cellular substrate for CD44-expressing cells)-mixed populations of CD133+/CD44+ or CD133-/CD44- cells. These data demonstrate that Matrigel modulates a stem cell phenotype and promotes tumor formation from SP and non-SP cells. The tumor micro-environmental niche and tumor cell to micro-environmental interactions may be important future targets for novel chemotherapeutic agents.

Effects of Wnt/β-catenin signaling pathway on the proliferation and invasive growth of cells in mantle cell lymphoma

Objective:To study the effects of Wnt/β-catenin signaling pathway on the proliferation and invasive growth of cells in mantle cell lymphoma.Methods: Patients who were diagnosed with mantle cell lymphoma by lymph node biopsy in Tongji Hospital? Tongji Medical College Huazhong University of Science & Technology between March 2015 and May 2017 were selected as lymphoma group of the research, and patients who were diagnosed with reactive hyperplasia by lymph node biopsy during the same period were selected as the control group. The protein expression of Wnt/β-catenin signaling pathway molecules in lymph node tissues were determined by enzyme-linked immunosorbent assay kit, and the mRNA expression of proliferation genes and invasion genes were determined by fluorescence quantitative PCR kit.Results:β-catenin, p-GSK-3β and Tcf/Lef protein levels as well as C-myc, CyclinD1, Est-1, MMP9 and MMP26 mRNA expression in lymph node tissues of lymphoma group were significantly higher than those of control group whereas DKK1 and WIF-1 protein levels as well as Bax, Apaf1, Caspase-3, TNFAIP3, TIMP2 and TIMP4 mRNA expression were significantly lower than those of control group. C-myc, CyclinD1, Est-1, MMP9 and MMP26 mRNA expression in lymphoma tissues were positively correlated withβ-catenin, p-GSK-3β and Tcf/Lef protein levels, and negatively correlated with DKK1 and WIF-1 protein levels;Bax, Apaf1, Caspase-3, TNFAIP3, TIMP2 and TIMP4 mRNA expression were negatively correlated withβ-catenin, p-GSK-3β and Tcf/Lef protein levels, and positively correlated with DKK1 and WIF-1 protein levels.Conclusion: The activation of Wnt/β-catenin signaling pathway can promote the proliferation and invasive growth of cells in mantle cell lymphoma.