Duxbury Mark S, Ito Hiromichi, Ashley Stanley W, Whang Edward E
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Biochem Biophys Res Commun. 2004 Apr 23;317(1):133-41. doi: 10.1016/j.bbrc.2004.03.018.
Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is an immunoglobulin superfamily member with a diversity of extracellular ligands that is implicated in the initiation and progression of a variety of malignancies. We sought to characterize the effects of CEACAM6 crosslinking on pancreatic adenocarcinoma cellular interaction with the extracellular matrix (ECM) components fibronectin and vitronectin. Antibody-mediated CEACAM6 crosslinking was performed and the ability of BxPC3 cells, which inherently overexpress CEACAM6, to adhere to fibronectin and vitronectin was quantified. The roles of the archetypal fibronectin (alpha5beta1 integrin) and vitronectin (alphavbeta3 integrin) receptors were determined. The effects of c-Src inhibition were investigated using the Src family kinase inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2) and c-Src specific RNA interference. CEACAM6 crosslinking initiates c-Src-dependent cross-talk between CEACAM6 and alphavbeta3 integrin, leading to increased ECM component adhesion. CEACAM6-mediated signaling events may contribute to the invasive and metastatic potential of pancreatic adenocarcinoma cells by promoting their interaction with ECM components.
癌胚抗原相关细胞黏附分子6（CEACAM6）是免疫球蛋白超家族成员，具有多种细胞外配体，与多种恶性肿瘤的发生和发展有关。我们试图描述CEACAM6交联对胰腺腺癌细胞与细胞外基质（ECM）成分纤连蛋白和玻连蛋白相互作用的影响。进行了抗体介导的CEACAM6交联，并对固有高表达CEACAM6的BxPC3细胞黏附于纤连蛋白和玻连蛋白的能力进行了定量。确定了典型的纤连蛋白（α5β1整合素）和玻连蛋白（αvβ3整合素）受体的作用。使用Src家族激酶抑制剂4-氨基-5-（4-氯苯基）-7-（叔丁基）吡唑并[3,4-d]嘧啶（PP2）和c-Src特异性RNA干扰研究了c-Src抑制的作用。CEACAM6交联引发CEACAM6与αvβ3整合素之间的c-Src依赖性串扰，导致细胞外基质成分黏附增加。CEACAM6介导的信号事件可能通过促进胰腺腺癌细胞与细胞外基质成分的相互作用，从而促进其侵袭和转移潜能。
