以整合素为靶点治疗乳腺癌的研究进展

乳腺癌是严重影响妇女身心健康甚至危及生命的最常见肿瘤之一,发病率占各种恶性肿瘤的7%～10%.乳腺癌通常发生于乳房腺上皮组织,绝经期前后的妇女发病率较高.男性乳腺癌罕见,仅占乳腺癌患者的1%～2%.整合素是细胞表面受体的主要家族,介导细胞和细胞外基质的黏附,介导细胞间的相互作用.整合素在生物体内广泛表达,在许多生命活动中发挥着关键的作用.整合素与癌症进程密切相关,在转移性肿瘤中某些整合素高表达,并与蛋白水解酶相互作用,导致基底膜降解.整合素通过重塑细胞外基质在肿瘤的迁移和侵袭中起着重要作用.综述了以整合素为靶点治疗乳腺癌的新进展.     

细胞粘附分子在食管癌中表达的研究进展

肿瘤的侵袭和转移对患者的生存起关键作用,直接影响外科手术的治愈率。侵袭和转移的发生,首先是瘤细胞从原发瘤分离,这是由于细胞与细胞、细胞与基质相互作用的调节异常所致,且其相互作用受某些细胞粘附分子的调节。本文简单地阐述了五种细胞粘附分子(钙粘素、整合素、CD44、免疫球蛋白超家族、选凝素),着重是它们在食管癌中的表达变化及其预后意义。     

整合素家族与肾小球系膜研究进展

整合素为一类位于细胞膜表面的糖蛋白分子，是细胞与细胞外基质（ＥＣＭ）相互作用的主要介导者。新近研究发现，整合素在维持肾小球组织的完整性和炎症、硬化过程中起重要作用。本文重点介绍整合素家族与肾小系膜的关系，包括其结构特性、表达调节和信号传递机制等等。     

CXCR7对HeLa细胞增殖、粘附和侵袭能力的影响

基质细胞衍生因子-1(SDF-1)在肿瘤侵袭、转移过程中起着重要的调控作用.此前认为SDF-1是通过其唯一受体CXCR4来起作用.近年来发现SDF-1还有另一作用受体——CXCR7,SDF-1/CXCR7在部分肿瘤侵袭转移过程中起重要作用,但其在宫颈癌HeLa细胞中的作用目前尚未明确.通过Western blotting检测HeLa细胞中CXCR4和CXCR7的表达,阻断CXCR4或CXCR7后,通过MTT法评价细胞增殖能力,细胞粘附实验评价细胞粘附能力,Transwell实验评价细胞侵袭能力.结果表明,CXCR4和CXCR7在HeLa细胞中表达.阻断CXCR4或CXCR7后,SDF-1诱导的HeLa细胞增殖、侵袭和与内皮细胞的粘附能力均被阻断.结果提示CXCR7在SDF-1诱导HeLa细胞增殖、侵袭和与内皮细胞的粘附过程中起着重要作用,将有望成为治疗宫颈癌转移的新靶点.     

微囊泡PKM2诱导单核/巨噬细胞分化促进肝癌进程

正肝细胞癌是一种高度恶性、容易复发、耐药性强且常在晚期确诊的原发性肝癌.肝癌肿瘤微环境对于肝癌发生发展至关重要,其中肿瘤浸润的单核/巨噬细胞是肝癌肿瘤微环境中最重要的基质细胞类型之一.理解肝癌细胞与肿瘤浸润的单核/巨噬细胞间的相互作用机制,寻找阻断两者相互作用的策略至关重要.肿瘤来源的胞外囊泡是肿瘤微环境中细胞间通讯的重要媒介.然而,肝癌细胞来源的胞外囊泡在介导肝癌细胞与肿瘤浸润的单核/巨噬细胞间通讯的作用机制及其对肝癌进程的影响尚不明确.2020年6月18日,吴乔教授课题组在Molecular     

环亲和素A的重组表达及其促进肝癌细胞侵袭转移的体外研究

为研究环亲和素A（CyclophilinA,CyPA）与肝癌转移的关系,用原核重组表达并纯化了CyPA。在不同浓度的CyPA刺激下,利用凝胶酶谱检测人肝癌细胞FHCC-98分泌基质金属蛋白酶（matrix metalloproteinases,MMPs）的能力。选择合适的刺激浓度,用BordenChamber检测肝癌细胞的侵袭能力。同时用抗CD147的抗体阻断CypA与其受体CD147的结合,检测阻断后FHCC-98在CyPA刺激下分泌MMPs及转移的能力。结果表明重组表达的CyPA能促进FHCC-98分泌激活或非激活形式的MMP-2并能促进FHCC-98的转移,而抗CD147的抗体能阻断其作用。实验结果表明：环亲和素A能与肝癌细胞表面的受体分子CD147结合,促进肝癌细胞的转移,提示其在“炎-癌”链中起到一定的作用。     

结直肠癌细胞过表达tricellulin促进人脐静脉内皮细胞侵袭转移

三细胞间紧密连接蛋白tricellulin在结直肠癌组织中高表达,且与结直肠癌的不良预后相关。血管生成是肿瘤侵袭转移的重要因素之一,血管内皮细胞在血管新生过程中起决定作用。研究tricellulin与内皮细胞的关系对探索肿瘤侵袭转移机制具有重要意义。本研究通过western blot观察结直肠癌细胞株与正常结肠上皮细胞株中tricellulin的差异表达,通过基因工程技术调控结直肠癌细胞HCT116中tricellulin的表达,transwell小室检测过表达tricellulin前后结直肠癌细胞侵袭能力变化及其上清液对人脐静脉内皮细胞（HUVEC）侵袭能力的影响,ELISA实验检测过表达tricellulin前后MMP2、MMP7的表达变化。结果显示：过表达tricellulin可增强HCT116细胞的侵袭能力,并且其上清液可增强HUVEC细胞的侵袭能力;过表达tricellulin可增加MMP2、MMP7的表达。说明人结直肠癌细胞过表达tricellulin可促进结直肠癌细胞侵袭迁移,并通过影响MMP2、MMP7的表达调控HUVEC细胞的侵袭转移。     

数据挖掘结合实验证明hsa-miR-371a-3p促进肝癌细胞迁移

肝细胞癌严重威胁着人类的生存,其转移是肝癌患者主要的死亡原因.microRNA参与调控肿瘤的转移,具有成为治疗靶点的潜力.本研究通过生物信息学的手段挖掘公共数据库中的microRNA表达谱数据,鉴定出新的潜在的促进肝癌转移的microRNA hsa-miR-371a-3p.细胞愈伤实验和细胞迁移实验的结果证明hsa-miR-371a-3p的过表达能够促进肝癌细胞的迁移.而且,在hsa-miR-371a-3p过表达的肝癌细胞中,预测的靶基因MRVI1和UBR7的mRNA表达水平下降,说明hsa-miR-371a-3p可能通过下调MRVI1和UBR7的方式促进肝癌细胞的迁移.     

CD44V6与消化道恶性肿瘤种植转移关系的细胞学研究

对消化道恶性肿瘤ＣＤ４４Ｖ６表达与腹腔术中脱落细胞、门静脉中转移癌细胞的相关性作了研究。发现ＣＤ４４Ｖ６与腹腔脱落细胞、门静脉中转移癌细胞相关。认为检测ＣＤ４４Ｖ６有助于了解消化道肿瘤的种植转移倾向。     

大蒜素对肺腺癌细胞侵袭生物学行为影响的初步研究

通过MTT法、细胞粘附试验、Transwell细胞迁移和侵袭试验检测不同浓度的大蒜素对肺腺癌细胞的活性、粘附、迁移与侵袭能力的变化;(RT-qPCR)逆转录-定量聚合酶链反应检测不同浓度的大蒜素对TIMP/MMP平衡的影响.本研究中发现大蒜素可呈剂量依赖性抑制肺腺癌细胞的活性、粘附、迁移和侵袭能力.大蒜素主要降低基质金...     

Expression, distribution and function of the focal adhesion kinase (pp125FAK) during murine ectoplacental cone outgrowthin vitro

Mouse embryo implantation is a complex process that includes trophoblast cells derived from ectoplacental cone (EPC) adhesion to and migration through the extracellular matrix (ECM) of uterine endometrium and invasion into the decidua. At the time of implantation, fibronectin (FN) is abundant in the decidua and is distributed pericellularly around each individual stromal cell, and its receptor (integrin α-5β-1) expression on trophoblast populations is up-regulated. The focal adhesion kinase, a 125 ku protein tyrosine kinase (pp125 FAK), is tyrosine phosphorylated upon integrin engagement with its ECM ligand, and its tyrosine phosphorylation sites then serve as the binding sites which couple it with cellular proteins that contain Src SH2 or SH3 domains. Through these linkages, pp125 FAK may integrate multiple signals triggered by integrins. The model of EPC culture %in vitro% was used to study the expression, distribution and function of pp125 FAK during EPC outgrowth on FN. Results indicated that, pp125 FAK primarily expressed and distributed in cellular focal adhesions of the front edge of trophoblast outgrowth from EPC, and was localized in the peripheral region of the individual migrating trophblast cell; antibody or antisense oligodeoxynucleotide to pp125 FAK inhibited EPC attachment and outgrowth, as well as trophoblast cells spreading and migration. This experiment demonstrated that pp125 FAK as an integrin-mediated signaling molecule was involved in EPC outgrowth %in vitro%, and played an important role during trophoblast cells interaction with FN.     

Clinical and pathological features of miR-10b and RHOC gene expression in hepatocellular carcinoma

Aberrant expression of microRNAs （miRNAs） was reported frequently in different human cancers. The major role of miRNA is targeting 31-UTR of coding gene and causing translational repression or mRNA degradation. miR-10b overexpression was reported to promote breast cancer metastasis by up-regulating RHOC expression. But its expression in hepatocellular carcinoma （HCC） remains unclear. Our study indicated that the expression of miR-10b was different in HCC and adjacent tissue samples, and reduced expression of miR-10b in HCC was related tovein invasion. High-level expression of RHOC was also related to vein invasion in HCC. But no correlation was found between miR-10b and RHOC expression. These results suggest that miR-10b and RHOC are independent predictors of HCC invasion and metastasis.     

Overexpression of PITPNM3 promotes hepatocellular carcinoma cell metastasis

A previous study indicated that C–C chemokine(C–C motif)ligand 18(CCL18)is capable of inducing tumor cell invasion and metastasis by interacting with receptor membrane-associated phosphatidylinositol transfer protein 3(PITPNM3)in breast cancer cells.The present study aims to investigate the correlation between the PITPNM3 expression and metastasis in hepatocellular carcinoma(HCC).Real-time quantitative polymerase chain reaction and Western blot were performed to detect the expression pattern of PITPNM3 in patient samples and HCC cell lines.Wound-healing and transwell chamber assays were performed to assess the migration and invasiveness of HCC cells,and the activation of the signaling protein downstream of PITPNM3 was also detected by Western blot and immunofluorescence.The results revealed that PITPNM3 was upregulated in HCC tissue compared to matched normal liver tissue.Silencing the expression of PITPNM3 by specific siRNAs markedly attenuated the invasive and metastatic abilities of HCC cells,whereas the upregulation of PITPNM3 significantly increased HCC cell mobility.Furthermore,inhibiting the expression of PITPNM3 suppressed the activation of Pyk2,FAK,and Src,while overexpression of PITPNM3enhanced the phosphorylation of FAK and Src in HCC cells.Besides,suppression of Pyk2 can also impair the clustering of integrin.These results imply that PITPNM3 is a vital determinant of HCC migration and invasion.     

自噬对肝癌SMMC-7721细胞侵袭迁移能力的影响

为探讨自噬对照射过程中肝癌SMMC-7721细胞侵袭和迁移能力的影响及其潜在的作用机制,将肝癌SMMC-7721细胞分为6组,分别为阴性对照(NC)组、8 Gy X-线照射(IR)组、自噬激活剂雷帕霉素(Rapa)组、自噬抑制剂三甲基腺嘌呤(3-MA)组、照射+雷帕霉素(IR+Rapa)组和照射+三甲基腺嘌呤(IR+3-MA)组,利用划痕实验和Transwell实验检测自噬对肝癌SMMC-7721细胞迁移和侵袭的影响;用CCK8实验检测照射、雷帕霉素和3-MA对肝癌细胞增殖的影响;用蛋白免疫印迹(Western blot)检测N-钙黏蛋白(N-cadherin)、波形蛋白(Vimentin)和LC3B蛋白表达情况。研究结果显示,照射可增强肝癌SMMC-7721细胞侵袭迁移的能力(P<0.05),同时,照射可抑制细胞的增殖能力(P<0.05);雷帕霉素激活自噬可增强细胞的侵袭迁移能力(P<0.05),3-MA抑制自噬可抑制细胞侵袭迁移和细胞的增殖能力(P<0.05)。照射可上调N-cadherin、Vimentin表达水平(P<0.05),激活或抑制自噬可分别增加或抑制N-cadherin、Vimentin蛋白表达水平(P<0.05)。表明X-线照射可激活自噬,促进细胞上皮-间充质转化(Epithelial-Mesenchymal Transition,EMT)的发生。激活自噬可以提高肝癌细胞上皮间质转化进而促进肝癌细胞侵袭迁移;反之,抑制自噬可阻碍肝癌细胞的侵袭迁移。     

乙酰肝素酶(HPSE)与肿瘤生长、转移关系的研究进展

目的:通过文献学习,了解乙酰肝素酶与肿瘤的生长和转移的关系。结论:1.乙酰肝素酶的表达(heparananse HPSE)通过降解硫酸乙酰肝素细胞(heparansulfate,HS)和降解硫酸乙酰肝素蛋白聚糖(heparansulfate proteoglycan,HSPG),破坏、改变细胞外基质(extracellular matrix,ECM)和基底膜(basement membranes,BM)结构,促进肿瘤细胞侵袭、转移。2.诱导血管的生成直接作用于内皮细胞以生芽方式促进血管生成,通过释放肿瘤微环境和ECM中储存的高活性的HS-bFGF复合物来诱发直接的血管反应,促进肿瘤的生长。乙酰肝素酶的表达是判断多种肿瘤预后的标记物之一。     

Regulated expression and binding of three VLA (beta 1) integrin receptors on T cells

Regulated adhesion of T cells to extracellular matrix (ECM) proteins is likely to be essential in T cell migration. Constitutive binding of various other cell types to ECM components is mediated by members of the VLA (very late antigen) subfamily of integrins. We describe here the regulated binding of resting CD4+ human T cells to ECM through three VLA integrins: VLA-4 and VLA-5 binding to fibronectin (FN), and a novel pathway of VLA-6 binding to laminin (LN). Binding to ECM is regulated in two ways. First, unlike other VLA-mediated interactions, VLA binding activity of the T cells is rapidly and dramatically augmented with cell activation without change in level of expression of the VLA molecules. Second, binding is regulated with T-cell differentiation; memory T cells express three- to four-fold more VLA-4, VLA-5, and VLA-6 than do naive cells, and bind more efficiently through them to FN and LN.     

Comparative study on the effect of integrin αvβ3 on secretion of matrix metalloproteinases in human normal and carcinoma trophoblasts

The invasion of cytotrophoblast cells into the maternal endometrium during embryonic implantation is very similar to the metastasis of carcinoma cells. However, the significant difference is that the former is a highly controlled process. In this report, the effects of integrin αvβ3 on the secretion of matrix metalloproteinase (MMP) were compared between normal cytotrophoblast cells and choriocarcinoma cells by RT-PCR, gelatin zymography and immunocytochemistry. The results reveal that both normal cytotrophoblast cells and choriocarcinoma cells can express integrin αvβ3. The secretion of MMPs in normal cytotrophoblast ceils is up-regulated by anti-αvβ3 antibody, whereas, decreased in choriocarcinoma cells. It was suggested that αvβ3 can modulate the expression of MMPs in trophoblasts, and this action is carried out through distinct mechanisms in normal and carcinoma cytotrophoblast cells.     

RAB5A在乳腺癌中的表达及转移相关性分析

目的 探讨RAB5A在乳腺癌转移中的作用与机制,以期为乳腺癌的基因治疗及研究提供新的靶点。方法 检测不同分化程度的乳腺癌组织标本中RAB5A蛋白的表达情况;应用FAM标记的RAB5A反义寡核苷酸,体外转染高转移度的乳腺癌细胞,观察肿瘤细胞的转移相关指标的变化。结果 乳腺癌组织中大多呈现不同程度RAB5A的表达,差异有显著性意义（P<0.05）,在浸润导管癌中RAB5A的表达程度与其他组织类分型差异有显著性意义（P<0.05）,肿瘤组织不同分化程度染色显示乳腺癌分化程度越低（P<0.05）,在细胞基底膜侵袭和运动实验中RAB5A反义核酸封闭后穿膜细胞数均明显减少。结论 RAB5A是一个可能与乳腺癌发生、转移相关的基因,并且还可能与它们的分化程度有关。RAB5A在人乳腺癌细胞的侵袭及转移特性的形成中具有重要的作用,RAB5A的反义分子能够有效地阻断该基因表达的翻译过程。