Vogelmann R, Kreuser E D, Adler G, Lutz M P
Department of Internal Medicine I, University of Ulm, Germany.
Int J Cancer. 1999 Mar 1;80(5):791-5. doi: 10.1002/(sici)1097-0215(19990301)80:5<791::aid-ijc25>3.0.co;2-4.
The factors that determine the metastatic behavior of pancreatic tumor cells are incompletely understood. In this study, we first demonstrate differences in adhesion properties, integrin expression and in vivo integrin function in the metastatic tumor cell line PaTu 8988s compared with the non-metastatic cell line PaTu 8988t. Both cell lines were derived from the same original tumor and exhibit identical genetic fingerprints. Using in vitro adhesion assays performed on purified extracellular matrix components, adhesion of PaTu 8988s cells was significantly increased on the basal membrane component laminin and decreased on the interstitial matrix protein fibronectin compared to PaTu 8988t cells. By immunocytochemistry and flow cytometry, and in correspondence with their adhesive properties, the metastatic PaTu 8988s cells did express a distinct pattern of integrin subunits. Laminin-binding integrins alpha6 and beta4 were overexpressed in PaTu 8988s cells. Fibronectin-binding alpha5 integrins were present at higher levels in the non-metastatic PaTu 8988t cells, whereas the beta1 subunit expression did not differ. Adhesion to laminin or fibronectin was specific and was mediated via integrins alpha6beta1 and alpha5beta1, respectively. In addition, metastasis formation in vivo after injection of cells into the tail vein of nude mice was inhibited by preincubation of PaTu 8988s cells with antibodies directed against the integrin alpha6 or beta1. We conclude that alpha6beta1 integrins are overexpressed and functionally active in metastatic human pancreatic carcinoma cells, and participate in metastasis formation probably through binding to the basal membrane component laminin.
决定胰腺肿瘤细胞转移行为的因素尚未完全明确。在本研究中，我们首先证明了与非转移性细胞系PaTu 8988t相比，转移性肿瘤细胞系PaTu 8988s在黏附特性、整合素表达及体内整合素功能方面存在差异。这两种细胞系均源自同一原发肿瘤，且具有相同的基因指纹。通过对纯化的细胞外基质成分进行体外黏附试验，发现与PaTu 8988t细胞相比，PaTu 8988s细胞在基底膜成分层粘连蛋白上的黏附显著增加，而在间质基质蛋白纤连蛋白上的黏附则减少。通过免疫细胞化学和流式细胞术，并与它们的黏附特性相对应，转移性PaTu 8988s细胞确实表达了一种独特的整合素亚基模式。与层粘连蛋白结合的整合素α6和β4在PaTu 8988s细胞中过表达。与纤连蛋白结合的α5整合素在非转移性PaTu 8988t细胞中的水平较高，而β1亚基的表达没有差异。对层粘连蛋白或纤连蛋白的黏附具有特异性，分别通过整合素α6β1和α5β1介导。此外，将PaTu 8988s细胞与针对整合素α6或β1的抗体预孵育后，可抑制将细胞注射到裸鼠尾静脉后在体内形成转移灶。我们得出结论，α6β1整合素在转移性人胰腺癌细胞中过表达且具有功能活性，可能通过与基底膜成分层粘连蛋白结合参与转移灶的形成。
