Interleukin-1α enhances integrin a6β1 expression and metastatic capability of human pancreatic cancer

被引:49
作者
Sawai, H [1 ]
Funahashi, H [1 ]
Yamamoto, M [1 ]
Okada, Y [1 ]
Hayakawa, T [1 ]
Tanaka, M [1 ]
Takeyama, H [1 ]
Manabe, T [1 ]
机构
[1] Nagoya City Univ, Grad Sch Med Sci, Dept Surg Gastroenterol, Mizuho Ku, Nagoya, Aichi 4678601, Japan
关键词
integrin; interleukin-1 receptor type I; metastasis; pancreatic carcinoma;
D O I
10.1159/000072343
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Objective: To investigate the mechanisms of metastasis formation in metastatic human pancreatic cancer, we examined the enhancement in integrin expression, and adherence to and invasiveness into extracellular matrix (ECM) proteins of human pancreatic cancer cells after exposure to interleukin (IL)-1alpha. Methods: Expression of IL-1 receptor type I (IL-1RI) and alterations in integrin subunits by IL-1alpha were examined by flow-cytometric analysis and by cellular enzyme-linked immunosorbent assay in four human pancreatic cancer cell lines (BxPC-3, PaCa-2, PANC-1, and SW1990), respectively. In addition, assays of cancer cell adhesion and invasion to ECM proteins were performed to investigate whether increased integrin expression affected the adhesive and invasive interaction between cancer cells and the putative integrin ECM ligands. Furthermore, immunohistochemistry was used to assess integrins and IL-1R1 expression in pancreatic tissues. Results: In metastatic cancer cells, expression of the alpha(6) subunit was enhanced by IL-1alpha treatment. While metastatic cancer cells exhibited preferential adherence to and invasion into laminin, these properties were enhanced by IL-1alpha. The alpha(6) subunit and IL-1RI were strongly expressed in pancreatic tissues from pancreatic cancer patients with liver metastasis. Conclusions: In pancreatic cancer, IL-1alpha enhanced alpha(6)beta(1)-integrin expression, probably via increased IL-1RI levels. Our results indicated that alpha(6)beta(1)-integrin and IL-1RI expression may play important roles in metastasis formation. Copyright (C) 2003 S. Karger AG, Basel .
引用
收藏
页码:167 / 173
页数:7
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