LIM1863 is useful to explore collective cancer cell migration,and the group of heterogeneous cells undergoing collective migration behaves like a supracellular unit

Collective cancer cell migration(CCCM)and epithelial-to-mesenchymal transition(EMT)play key roles in metastasis.This study reports that the colorectal carcinoma cell line LIM1863 is useful for the study of CCCM and EMT.Methods:Hematoxylin and eosin staining,scanning electron microscopy,transmission electron microscopy,and western blot analysis were performed.Results:LIM1863 automatically grew as spheroids in suspension and had important typical epithelial properties,including several layers of cells arranged around a central lumen,apical-basal polarity,and types of cell-cell junctions.Treatment with a combination of both TGF beta 1 and TNF alpha induced definite and distinct EMT,a spheroid changing phenotype to form a monolayer high-confluent patch without lumen,without polarity.Spontaneous CCCM occurred in spheroids.Flat EMT cells adhered to the base of a dish,exhibited persistent movement as a cluster of cells,and then shed,resulting in a cluster.All cells from one cluster undergoing CCCM died.Otherwise,all cells undergoing EMT disappeared and almost all cells located in the cell reservoir survived and proliferated.Conclusion:LIM1863 is an excellent cell line to study CCCM and EMT.The group of heterogeneous cells undergoing CCCM behaves like a supracellular unit.

Paxillin serine 178 phosphorylation in control of cell migration and metastasis formation through regulation of EGFR expression in breast cancer

Aim:Paxillin is a well-known multidomain scaffold protein that is involved in the regulation of cell-matrix adhesion dynamics,a process required for the tumor cell migration and invasion.Phosphorylation of the serine residue 178 requires c-Jun NH2-terminal kinase(JNK)activation,which occurs downstream of epidermal growth factor receptor(EGFR)-mediated signaling and drives cell migration.In this study,we investigated the significance of paxillin Ser178 phosphorylation in breast cancer progression.Methods:We employed the rat mammary carcinoma MTLn3 cell line with which we established stabile variants of both wild type and mutant GFP-paxillin constructs.With those,we next performed several in vitro assays including cell proliferation,migration and focal adhesion dynamics.Finally,we monitored the metastatic spread of both cell line variants in an othrotopic mouse model for breast cancer.Results:Here we show that expression of the phospho-defective mutant paxillinS178A in the metastatic mammary adenocarcinoma MTLn3 cell-line significantly decreased EGF-induced cell migration,which was correlated with impaired focal adhesion dynamics.Moreover,paxillinS178A attenuated lung metastasis formation in an orthotopic in vivo mammary gland tumor/metastasis model,demonstrating the importance of JNK-mediated paxillin phosphorylation in breast cancer progression.Expression of paxillinS178A caused a decrease in EGFR expression, ;while re-expression of EGFR in MTLn3-paxillinS178A cells fully restored EGF-driven cell motility and focal adhesion dynamics.Furthermore,re-expression of EGFR in MTLn3-paxillinS178A rescued spontaneous metastasis from breast to lung.Conclusion:Overall our data show an important role for JNK-mediated paxillin Ser178 phosphorylation in the regulation of EGFR expression and thereby,in EGF-driven cell migration and metastasis formation.

Regulation of tumor cell migration by protein tyrosine phosphatase (PTP)-proline-, glutamate-, serine-,and threonine-rich sequence(PEST)

Protein tyrosine phosphatase (PTP)-proline-,glutamate-,serine-,and threonine-rich sequence (PEST) is ubiquitously expressed and is a critical regulator of cell adhesion and migration.PTP-PEST activity can be regulated transcriptionally via gene deletion or mutation in several types of human cancers or via post-translational modifications,including phosphorylation,oxidation,and caspase-dependent cleavage.PTP-PEST interacts with and dephosphorylates cytoskeletal and focal adhesion-associated proteins.Dephos-phorylation of PTP-PEST substrates regulates their enzymatic activities and/or their interaction with other proteins and plays an essential role in the tumor cell migration process.

Inhibitory Effect of Cigarette Smoke Extract on Experimental Lung Metastasis of Mouse Melanoma by Suppressing Tumor Invasion

We investigated the effect of a nicotine-and tar-free cigarette smoke extract (CSE) using an experimental metastasis mouse model which was intravenously injected with B16-BL6 mouse melanoma cells. Three-hour pretreatment of cells with various concentrations of CSE (0, 0.1, 0.3, and 1%) dose-dependently reduced the number of lung metastatic nodules 14 days after tumor injection. To elucidate the mechanism of this anti-metastatic effect of CSE, we examined the invasion and migration activities of B16-BL6 cells pretreated with CSE for three hours in vitro. CSE significantly reduced the invasion of cells at 1% and the migration at 0.3% and 1%. Under the same pretreatment conditions, CSE had no effect on the proliferation of cells. These findings suggest that CSE contains some ingredients that suppress hematogenic lung metastasis via inhibition of the invasion and migration activities of mouse melanoma cells.

Extracellular viscosity:a potential therapeutic target to combat cancer metastasis

Aberrant migration plays a key role in cancer development and is particularly significant during invasion,which is the initial step of metastasis.Research over the past decade has shown that cancer cell migration is affected by several physical stimuli within the tumor microenvironment.For example,tumor metastasis is driven by interstitial flow caused by high intertumoral interstitial fluid pressure1.Shellard et al.showed that cells follow gradients in the stiffness of the substrates to prompt collective cell migration in vitro2.However,the effect of extracellular viscosities on cell function remains unclear.

Expression of aquaporin-1 in SMMC-7221 liver carcinoma cells promotes cell migration

Migration of tumor cells is a crucial step in tumor invasion and metastasis. Here we provide evidence that aquaporin expression is involved in tumor cell migration. RT-PCR, immunofluorescence and Western blot analysis demonstrated the AQP1 protein expression on the plasma membrane of SMMC-7221 human hepatoma cells. SMMC-7221 cell clones with high (SMMC-7221hPf) and low (SMMC-7221lPf) water permeability were identified by functional assays with corresponding high and low AQP1 expression. Cell migration rate was remarka- bly higher in SMMC-7221hPf cells than SMMC-7221l Pf cells, assessed by Boyden chamber and wound healing assays, whereas cell growth and adhesion were not different. Adenovirus-mediated AQP1 ex- pression in SMMC-7221lPf cells increased their water permeability and migration rate. These results pro- vide the first evidence that aquaporin-mediated membrane water permeability enhances tumor cell migration and may be associated with tumor invasion and metastasis.

Reprogramming of cancer-associated fibroblasts by apoptotic cancer cells inhibits lung metastasis via Notch1-WISP-1 signaling

The interplay between apoptotic cancer cells and the tumor microenvironment modulates cancer progression and metastasis.Cancer-associated fibroblasts(CAFs)play a crucial role in promoting these events through paracrine communication.Here,we demonstrate that conditioned medium(CM)from lung CAFs exposed to apoptotic cancer cells suppresses TGF-β1-induced migration and invasion of cancer cells and CAFs.Direct exposure of CAFs to apoptotic 344SQ cells(ApoSQ)inhibited CAF migration and invasion and the expression of CAF activation markers.Enhanced secretion of Wnt‐induced signaling protein 1(WISP-1)by CAFs exposed to ApoSQ was required for these antimigratory and anti-invasive effects.Pharmacological inhibition of Notch1 activation or siRNA-mediated Notch1 silencing prevented WISP-1 production by CAFs and reversed the antimigratory and anti-invasive effects.Enhanced expression of the Notch ligand delta-like protein 1 on the surface of ultraviolet-irradiated apoptotic lung cancer cells triggered Notch1-WISP-1 signaling.Phosphatidylserine receptor brain-specific angiogenesis inhibitor 1(BAI1)-Rac1 signaling,which facilitated efferocytosis by CAFs,participated in crosstalk with Notch1 signaling for optimal production of WISP-1.In addition,a single injection of ApoSQ enhanced WISP-1 production,suppressed the expression of CAF activation markers in isolated Thy1^(+)CAFs,and inhibited lung metastasis in syngeneic immunocompetent mice via Notch1 signaling.Treatment with CM from CAFs exposed to ApoSQ suppressed tumor growth and lung metastasis,whereas treatment with WISP-1-immunodepleted CM from CAFs exposed to ApoSQ reversed the antitumorigenic and antimetastatic effects.Therefore,treatment with CM from CAFs exposed to apoptotic lung cancer cells could be therapeutically applied to suppress CAF activation,thereby preventing cancer progression and metastasis.

TRIP13 is identified as a prognosis biomarker for renal clear cell carcinoma and promotes renal cell carcinoma cell proliferation, migration and invasion

This work aimed to discover new therapeutic targets in renal clear cell carcinoma by bioinformatics and detect the effect of candidate gene TRIP13 in renal cell carcinoma(RCC)cell proliferation,migration,and invasion.Differentially expressed mRNAs were screened based on The Cancer Genome Atlas(TCGA)-Kidney Renal Clear Cell Carcinoma(KIRC)databases,and functional enrichments,survival analysis,receiver operating characteristic curve(ROC),and Protein–Protein Interaction(PPI)protein interaction analysis were performed by R software to screen the candidate gene TRIP13.Then,the expression of candidate gene TRIP13 in 92 pairs of cancer and adjacent normal tissues of renal clear cell carcinoma patients were detected by qRT-PCR,western blotting,and immunochemical analysis.The TRIP13 level and clinicopathological characteristics of patients with renal clear cell carcinoma were analyzed.Using 186-O and ACHN RCC cell lines with TRIP13 overexpressing or downregulating,the effect of TRIP13 on cell viability and proliferation were detected by CCK8 and EdU staining,respectively.The migration and invasion were detected by Transwell assays.A total of 19858 differentially expressed genes,5823 differentially expressed genes,3657 up-regulated genes,and 2166 down-regulated genes were identified.TRIP13 was closed associated with cell cycle regulation,and survival and prognosis of renal clear cell carcinoma were selected as a candidate gene.The mRNA and protein levels of TRIP13 in cancer tissues were higher than that in adjacent normal tissues.TRIP13 level was significantly associated with tumor size,tumor stage,Fuhrman grade,and lymph node metastasis.TRIP13 overexpression significantly increased cell viability,proliferation,migration,and invasion,while downregulating of TRIP13 had opposite effects in both 186-O and ACHN cells.Therefore,TRIP13 promotes RCC proliferation and metastasis,which should be a novel biomarker for early diagnosis,treatment,and prognosis of RCC.

A new protein Girdin in tumor metastasis

The phosphatidylinositol 3-kinase/Akt serine/threonine kinase system regulates multiple cellular processesthrough the phosphorylation of a great number of downstream substrates and has been recognized as an important pathway for signal transduction, and in cancer invasion and metastasis.1 Although it is accepted that Akt promotes the metastasis of human malignant tumors, the mechanisms of Akt function to promote cell migration remains to be elucidated. Girdin,

Anti-tumor activity of rice bran hydrolysates on migration, invasion and angiogenesis

Objective:To investigate anti-tumor effect of rice bran hydrolysates(RBH)on proliferation,migration,invasion,and angiogenesis of cholangiocarcinoma(CCA)cells,and elucidate the underlying mechanisms.Methods:RBH was prepared from Tubtim Chumprae rice(Oryza sativa L.)by hydrothermolysis followed by protease digestion.Phenolic content in RBH was analyzed by high-performance liquid chromatography.Human CCA cells,KKU-156,KKU-452,and KKU-100,were used to study the effects of RBH on proliferation,migration,invasion,and adhesion by wound healing,Transwell chamber,and fibronectin cell adhesion assays.Angiogenesis was evaluated using human umbilical vein endothelial cells.Proteins associated with cancer progression were analyzed by immunobloting assays.Results:RBH contained carbohydrates,proteins,lipids,and various phenolic compounds and flavonoids.RBH did not inhibit CCA proliferation,but strongly suppressed migration,invasion,adhesion of CCA cells,and the formation of tube-like capillary structures of human umbilical vein endothelial cells.Moreover,RBH downregulated phosphorylation of FAK,PI3K,and Akt,suppressed NF-κB nuclear translocation,decreased the expression of ICAM-1,vimentin and vascular endothelium growth factor(VEGF),and increased the expression of E-cadherin.Conclusions:RBH suppresses CCA cell migration and invasion and decreases expression of proteins involved in cancer metastasis.RBH is a potential food supplement for cancer prevention.

Dissecting brain tumor growth and metastasis in vitro and ex vivo

Local infiltration and distal dissemination of tumor cells hamper efficacy of current treatments against central nervous system(CNS)tumors and greatly influence mortality and therapy-induced long-term morbidity in survivors.A number of in vitro and ex vivo assay systems have been established to better understand the infiltration and metastatic processes,to search for molecules that specifically block tumor cell infiltration and metastatic dissemination and to pre-clinically evaluate their efficaciousness.These systems allow analytical testing of tumor cell viability and motile and invasive capabilities in simplified and well-controlled environments.However,the urgent need for novel anti-metastatic therapies has provided an incentive for the further development of not only classical in vitro methods but also of novel,physiologically more relevant assay systems including organotypic brain slice culture.In this review,using publicly available peer-reviewed primary research and review articles,we provide an overview of a selection of in vitro and ex vivo techniques widely used to study growth and dissemination of primary metastatic brain tumors.Furthermore,we discuss how our steadily increasing knowledge of tumor biology and the tumor microenvironment could be integrated to improve current research methods for metastatic brain tumors.We believe that such rationally improved methods will ultimately increase our understanding of the biology of brain tumors and facilitate the development of more efficacious anti-metastatic treatments.

piR-823在宫颈鳞癌中的表达及对侵袭、转移的影响

目的探讨宫颈鳞状细胞癌(CSCC)中PIWI相互作用RNA(piR)-823的表达、与临床病理特征的关系及对侵袭、转移的影响。方法收集2019年1月至2021年12月95例CSCC手术切除标本及配对癌旁组织。采用piRNA表达谱芯片技术获取5例CSCC中差异表达的piRNA表达谱。在宫颈癌细胞株C33A和HeLa中分别转染piR-823-mimic质粒(piR-823过表达组)、阴性对照质粒(对照组)、si-piR-823质粒(piR-823干扰组)和si-对照组质粒(si-对照组)。采用实时荧光定量聚合酶链反应(qPCR)检测piR-823表达水平,Transwell小室实验检测piRNA-823对CSCC细胞侵袭的影响。生物信息学预测piR-823下游靶基因,采用qPCR和Western blotting检测piR-823表达水平对靶基因mRNA和蛋白表达的影响。裸鼠肺转移成瘤实验观察piR-823对CSCC细胞肺转移的影响。结果CSCC的piRNA表达谱中符合条件且表达上调的piRNA共有5个,在95例CSCC组织中piR-823和piR-37390表达上调得到了验证,选择上调倍数更高的piR-823作为研究对象。piR-823表达与CSCC病理分级和淋巴结转移有关(P<0.05),而与年龄、HPV感染、肿瘤大小和TNM分期无关(P>0.05)。Transwell小室实验显示,过表达piR-823能促进CSCC细胞的侵袭,而干扰piRNA-823表达能抑制CSCC细胞的侵袭(P<0.05)。qPCR和Western blotting检测显示,过表达piR-823抑制了其下游靶基因磷酸甘油酸脱氢酶(PHGDH)的mRNA和蛋白表达,而干扰piR-823表达则提高了PHGDH的mRNA和蛋白表达(P<0.05)。裸鼠肺转移成瘤实验表明,干扰piR-823表达后肺转移瘤数目明显减少(P<0.05)。结论在CSCC组织中piR-823表达水平上调。piR-823可能通过抑制PHGDH的mRNA和蛋白表达,从而促进了CSCC细胞的侵袭和转移。

长链非编码RNA-PVT1促进肾癌细胞的迁移和转移

目的探讨长链非编码RNA-PVT1(Lnc-PVT1)在透明细胞肾细胞癌(ccRCC)中的表达水平及临床意义。方法收集69对ccRCC组织和癌旁正常组织。采用实时荧光定量聚合酶链反应(qRT-PCR)检测Lnc-PVT1在ccRCC中的表达水平。应用RNA原位杂交(RISH)技术测定ccRCC中Lnc-PVT1阳性表达情况。采用Transwell实验分析ccRCC细胞迁移的数目变化。通过生物信息学预测Lnc-PVT1和微小RNA-145(miR-145)的下游靶基因,并通过实验加以验证。采用Rescue回复实验分析Lnc-PVT1对miR-145/基质金属蛋白酶-9(MMP9)通路和迁移的影响。结果qRT-PCR结果显示,Lnc-PVT1在ccRCC组织和细胞中表达水平升高(P<0.05)。RISH实验提示,Lnc-PVT1在ccRCC组织中呈阳性表达。ccRCC组织Lnc-PVT1阳性率为73.91%(51/69),高于癌旁正常组织的14.49%(10/69),差异有统计学意义(χ^(2)=4.128,P<0.05)。Lnc-PVT1的阳性表达与ccRCC病理分级和淋巴结转移相关(P<0.05),而与患者年龄、性别、肿瘤大小和TNM分期无关(P>0.05)。Transwell迁移实验结果表明,过表达Lnc-PVT1促进ccRCC细胞迁移能力,降低Lnc-PVT1表达抑制ccRCC细胞迁移能力(P<0.05)。miR-145是Lnc-PVT1调控的靶基因;miR-145下游直接靶基因是MMP9。Lnc-PVT1能抑制miR-145表达,促进MMP9蛋白表达。结论Lnc-PVT1通过miR-145/MMP9通路促进肾癌细胞的迁移和转移,或可为治疗转移性肾细胞癌提供可能的分子靶点和依据。

卵巢上皮性癌转移的关键基因筛选与功能分析

目的:筛选卵巢上皮性癌(卵巢癌)转移的关键基因,并基于卵巢癌细胞株SKOV3,探索其对卵巢癌细胞迁移侵袭的影响。方法:基于癌症基因组图谱(TCGA)数据库、基因表达综合(GEO)数据库及人类基因数据库(GeneCards),通过limma差异表达分析及Kaplan-Meier生存分析挖掘在卵巢癌中高表达且与患者不良预后相关的迁移侵袭相关基因,并通过基因本体(GO)功能富集分析预测基因参与的生物学过程。利用PXN敲减慢病毒感染SKOV3细胞后,通过细胞划痕实验和Transwell迁移侵袭实验探讨PXN敲减对卵巢癌细胞迁移和侵袭能力的影响。利用癌症药物敏感性基因组学(GDSC)数据库对样本的化疗反应进行预测,评估PXN基因的卵巢癌细胞化疗敏感性的影响。结果:共筛选到36个迁移侵袭相关基因在卵巢癌组织中高表达,其中PXN基因高表达与卵巢癌患者不良预后相关(P<0.05)。PXN的功能与组蛋白修饰、染色质共价修饰、赖氨酸肽基修饰、蛋白质去泛素化、通过去除小蛋白进行蛋白质修饰、组蛋白去泛素化以及组蛋白H3-K4三甲基化等相关。荧光显微镜、Western blot结合RT-qPCR结果显示,在SKOV3细胞中成功敲减PXN基因。细胞功能学实验表明,PXN敲减组相对于空白对照组和阴性对照组,划痕愈合面积更小,穿膜细胞数更少。PXN高表达组中的顺铂及紫杉醇IC 50明显高于PXN低表达组(P<0.001),而其吉西他滨及多柔比星的IC 50明显低于PXN低表达组(P<0.0001)。肿瘤细胞中紫杉醇的IC 50明显低于正常卵巢细胞(P<0.0001),其西他滨及多柔比星的IC 50值高于正常卵巢细胞(P<0.0001)。结论:迁移侵袭相关基因PXN在卵巢癌中高表达,且与患者不良预后相关。PXN表达水平降低能抑制卵巢癌细胞SKOV3的迁移和侵袭。PXN基因表达水平与卵巢癌细胞对化疗药物的敏感性相关。

Inhibiting calcium-activated chloride channel ANO1/TMEM16A suppresses migration of tumor epithelial cells

不受控制的细胞迁移是肿瘤转移和形成的一个共同特征。了解细胞迁移过程中的重要分子靶点可以帮助我们开发控制侵袭性肿瘤细胞的新型治疗策略。在本研究中,我们发现钙激活氯通道ANO1/TMEM16A在细胞的迁移中扮演了重要角色,抑制ANO1离子通道功能能够使肿瘤细胞的迁移受到抑制。在肿瘤细胞系中,通过sh RNA沉默ANO1的表达可以抑制细胞的迁移和侵袭能力。同时,ANO1特异性抑制剂T16Ain-A01可以发挥显著减慢肿瘤细胞迁移和侵袭速度的药理作用,并且这种作用的大小依赖于T16Ain-A01使用剂量。综上所述,钙激活氯通道ANO1与细胞迁移密切相关,研究Ca CC抑制剂将有助于开发针对癌症转移的创新疗法。

养正消积抗肿瘤作用的机制

养正消积胶囊是在络病理论指导下由黄芪、女贞子等16味药组成的方剂,研究表明其提取物DME25具有抑制肿瘤细胞粘附、迁移,血管生成以及肿瘤细胞与间皮细胞粘附的功效,但尚需进一步的成份提纯以及研究证实其在肿瘤治疗中的临床价值。本文主要对养正消积胶囊的成份以及药效、成份的提取以及成份的鉴定、对肿瘤细胞的作用、对肿瘤血管生成的作用及对体内肿瘤的作用进行综述。

水通道蛋白-依赖性细胞迁移的研究进展

水通道蛋白(AQPs)是一类介导跨膜水运输的内在蛋白。近年来,一些研究成果证实,AQP具有介导细胞迁移的功能。该文综述了各种不同类型的AQPs-依赖性细胞迁移(AQPs-dependent cell migration):AQP1促进内皮细胞迁移;AQP4促进星形胶质细胞迁移;AQP3促进角膜上皮细胞、肠上皮细胞、皮肤角质形成细胞的迁移。此外,AQPs还能促进肿瘤细胞的迁移,增加肿瘤细胞的转移潜能。AQPs介导的细胞迁移与许多疾病有着内在联系,调控AQP的表达是一种尚待开发的治疗手段。

肿瘤细胞粘附、迁移与转移的相关性

肿瘤细胞的粘附、迁移能力与癌转移密切相关．细胞粘附分子选择素、整合素、免疫球蛋白超家族及钙粘素介导同型或异型细胞间以及细胞与基质间的粘附，其在肿瘤细胞表面表达数量或分布方式的改变直接或间接影响着转移潜能，是肿瘤细胞从原发瘤脱落以及着床的关键性环节．肿瘤细胞的迁移能力被认为是癌转移的限速环节．一般情况下，肿瘤细胞在体内或体外的迁移能力与其转移潜能呈正相关性，肿瘤细胞通过对迁移刺激物的趋化性及趋触性应答而完成向远离器官的转移。

斑蝥素抑制人高转移卵巢癌细胞HO-8910PM侵袭转移的体外实验研究

背景与目的:斑蝥素在治疗癌症方面显示出其独特的疗效,已有较多文献证实核因子鄄κB(nuclearfactor鄄kappaB,NF鄄资B)与肿瘤侵袭转移关系密切。本研究旨在观察斑蝥素对人高转移卵巢癌细胞HO鄄8910PM转移相关能力的影响,并探讨其作用机理。方法:MTT法及细胞粘附人工重组基底膜实验检测斑蝥素对HO鄄8910PM细胞的细胞毒作用及粘附能力的影响;用Transwell小室法检测斑蝥素对HO鄄8910PM细胞侵袭能力和趋化运动能力的影响;Westernblot法分析斑蝥素对HO鄄8910PM细胞中NF鄄κB和血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)的影响。结果:20μmol/L的斑蝥素作用6h对HO鄄8910PM细胞抑制率及体外侵袭、趋化运动和粘附的抑制率分别为(8.4±2.2)%及(38.8±1.7)%、(40.3±5.6)%和(55.1±6.7)%。20μmol/L斑蝥素能明显下调HO鄄8910PM细胞中NF鄄κB和VEGF的表达。结论:斑蝥素能抑制HO鄄8910PM细胞的侵袭、运动和粘附能力。斑蝥素抗肿瘤侵袭转移的作用机制与NF鄄κB和VEGF蛋白的表达下调有关。

胞外酸性与肿瘤的浸润转移

组织缺氧是实体瘤的一个主要特征,它引起肿瘤细胞胞外酸性环境的形成.肿瘤细胞通过质子感知的G蛋白偶联受体(G protein-coupled receptors,GPCRs)或质子感知的离子通道感知其胞外的酸性环境,并激活多条细胞内信号通路,影响细胞功能.肿瘤最致命的方面在于其转移能力,肿瘤转移程度与肿瘤细胞迁移能力呈正相关.因此,对胞外酸性与肿瘤细胞迁移扩散之间关系的深入研究将有助于发现更多新的抗肿瘤转移药物.本文就肿瘤酸性微环境的形成、肿瘤细胞的质子感知机制、胞外酸性环境对肿瘤浸润转移的影响及如何将肿瘤pH调节应用于癌症治疗等方面的内容予以综述.