Signaling by epidermal growth factor differentially affects integrin-mediated adhesion of tumor cells to extracellular matrix proteins

Signaling by epidermal growth factor differentially affects integrin-mediated adhesion of tumor cells to extracellular matrix proteins
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表皮生长因子的信号传导对整合素介导的肿瘤细胞与细胞外基质蛋白的粘附有不同的影响

DOI:
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发表时间:
1996
期刊:
Journal of molecular medicine
影响因子:
--
通讯作者:
R. Lichtner
R. Lichtner
中科院分区:
--
文献类型:
--
作者:
Elke Genersch;Detlef Schuppan;R. Lichtner

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摘要表皮生长因子(EGF)影响不同表皮生长因子受体(EGFR)表达细胞系与不同细胞外基质(ECM)蛋白的粘附。 为了研究EGFR和整合素之间的假定受体串扰,我们选择了两种细胞系进行更详细的分析:高转移性大鼠乳腺癌克隆MTLn 3,其在10 ng/ml EGF存在下显示出与ECM蛋白的粘附增加,而非转移性人外阴癌细胞系A431在相同条件下显示出粘附减少。在几分钟内观察到这些EGF介导的对粘附的刺激或抑制作用。对人A431细胞的抑制作用被干扰配体结合的EGFR特异性抗体阻断。在二价阳离子MTLn 3和A431细胞的存在下进行的细胞粘附试验中表现出典型的行为描述的整合素依赖性基质粘附:Mn 2+增强结合胶原蛋白IV和纤连蛋白,而Ca 2+抑制粘附胶原蛋白IV,但不纤连蛋白。使用抗人整联蛋白抗体的粘附抑制试验显示,A431细胞通过α1β1和α2β1粘附于胶原蛋白,并且粘附于纤连蛋白主要通过α5β1介导。MTLn 3细胞与纤连蛋白的相互作用部分依赖于RGD,表明α3β1或α5β1参与。在这些试验中加入EGF表明,通过加入二价阳离子、RGD肽或功能阻断整联蛋白抗体来影响整联蛋白胞外结构域并不能阻止EGF介导的作用。我们的结论是,EGFR的下游信号可以调节整合素介导的粘附ECM蛋白的抑制和刺激的方式。
Abstract The adhesion of different epidermal growth factor (EGF) receptor (EGFR) expressing cell lines to various extracellular matrix (ECM) proteins is influenced by EGF. To investigate a putative receptor cross-talk between EGFR and integrins we chose two cell lines for a more detailed analysis: the highly metastatic rat mammary carcinoma clone MTLn3 that showed increased adhesion to a panel of ECM proteins in the presence of 10 ng/ml EGF and the nonmetastatic human vulva carcinoma cell line A431 which showed a decreased adhesion under the same conditions. These EGF-mediated stimulatory or inhibitory effects on adhesion were observed within a few minutes. On human A431 cells the inhibitory effect was blocked by an EGFR-specific antibody that interferes with ligand binding. In cell adhesion assays performed in the presence of divalent cations MTLn3 and A431 cells exhibited the typical behavior described for integrin-dependent matrix adhesion: Mn2+ enhanced binding to collagen IV and fibronectin whereas Ca2+ inhibited adhesion to collagen IV but not to fibronectin. Adhesion-inhibition assays with anti-human integrin antibodies revealed that A431 cells adhere to collagen via α1β1 and α2β1, and that adhesion to fibronectin is mediated predominantly through α5β1. The interaction of MTLn3 cells with fibronectin was in part RGD dependent, indicating the involvement of either α3β1 or α5β1. Addition of EGF in these assays showed that affecting the integrin extracellular domains by addition of either bivalent cations, RGD peptides, or function-blocking integrin antibodies did not prevent the effects mediated by EGF. We conclude that signals downstream of EGFR can modulate integrin-mediated adhesion to ECM proteins in both an inhibitory and a stimulatory manner.
DOI: 10.1073/pnas.92.15.6981
发表时间: 1995-07-18
影响因子: 11.1
作者:
MAA, MC;LEU, TH;PARSONS, SJ
通讯作者: PARSONS, SJ
DOI: --
发表时间: 1993-09
期刊: Cancer research
影响因子: 11.2
作者:
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通讯作者: Zhen Fan;Hideo Masui;Ian Altas;John Mendelsohn
DOI: 10.1091/mbc.6.10.1349
发表时间: 1995-10-01
影响因子: 3.3
作者:
PLOPPER, GE;MCNAMEE, HP;INGBER, DE
通讯作者: INGBER, DE
碱性成纤维细胞生长因子促进来自鸡神经管的神经上皮细胞与培养物中的细胞外基质蛋白的粘附相互作用。
DOI: 10.1242/dev.119.3.943
发表时间: 1993
期刊: Development (Cambridge, England)
影响因子: --
作者:
Kinoshita,Y;Kinoshita,C;Heuer,JG;Bothwell,M
通讯作者: Bothwell,M
DOI: 10.1006/excr.1993.1304
发表时间: 1993-12-01
影响因子: 3.7
作者:
CHEN, JD;ZHANG, K;KIM, JP
通讯作者: KIM, JP