Sawai H, Yamamoto M, Okada Y, Sato M, Akamo Y, Takeyama H, Manabe T
First Department of Surgery, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 4678601, Japan.
Pancreas. 2001 Nov;23(4):399-405. doi: 10.1097/00006676-200111000-00011.
Adhesion of tumor cells to extracellular matrix (ECM) proteins plays an important role in tumor invasion and metastasis.
To investigate the expression of integrins in human pancreatic cancer cell lines and its alteration by interleukin (IL)-1alpha to examine the mechanism of adhesion of metastatic human pancreatic cancer cells to ECM proteins.
The expression of integrin subunits and their alteration by IL-1alpha were examined by flow-cytometric analysis and cellular enzyme-linked immunosorbent assay in three metastatic human pancreatic cancer cell lines (AsPC-1, BxPC-3, and SW1990) and two nonmetastatic cancer cell lines (PaCa-2 and PANC-1). In addition, assays of cancer cell adhesion to ECM proteins were performed to investigate if increased integrin expression actually affected the adhesive interaction between cancer cells and the putative integrin ECM ligands.
The alpha(6) subunit expressed in metastatic cancer cells was enhanced by IL-1alpha. Metastatic cancer cells also showed preferential adherence to laminin compared with nonmetastatic cancer cells, and this was enhanced by IL-1alpha.
In pancreatic cancer, the enhancement of alpha(6)beta(1) integrin by IL-1alpha through IL-1 receptor type I, as well as the expression of alpha(6)beta(1) integrin, plays an important role in metastasis formation.
肿瘤细胞与细胞外基质(ECM)蛋白的黏附在肿瘤侵袭和转移中起重要作用。
研究整合素在人胰腺癌细胞系中的表达及其受白细胞介素(IL)-1α的影响,以探讨转移性人胰腺癌细胞与ECM蛋白黏附的机制。
采用流式细胞术分析和细胞酶联免疫吸附测定法,检测三种转移性人胰腺癌细胞系(AsPC-1、BxPC-3和SW1990)和两种非转移性癌细胞系(PaCa-2和PANC-1)中整合素亚基的表达及其受IL-1α的影响。此外,进行癌细胞与ECM蛋白黏附试验,以研究整合素表达增加是否真的影响癌细胞与假定的整合素ECM配体之间的黏附相互作用。
IL-1α增强了转移性癌细胞中α(6)亚基的表达。与非转移性癌细胞相比,转移性癌细胞对层粘连蛋白也表现出优先黏附,且IL-1α增强了这种黏附。
在胰腺癌中,IL-1α通过I型IL-1受体增强α(6)β(1)整合素的表达,以及α(6)β(1)整合素本身的表达,在转移形成中起重要作用。