Relationship between Enhancement of Integrins by Interleukin-1 alpha and Metastasis in Pancreatic Cancer Cells

Hirozumi Sawai, Minoru Yamamoto, Hitoshi Funahashi, Mikinori Sato, Yuji Okada, Tetsushi Hayakawa, Moritsugu Tanaka, Yoshimi Akamo, Hiromitsu Takeyama and Tadao Manabe

First Department of Surgery, Nagoya City University Medical School

Background: Tumor cell adhesion to extracellular matrix (ECM) proteins plays an important role in tumor invasion and metastasis. We studied integrin expression in human pancreatic cancer cell lines and its alteration by Interleukin-1α (IL-1α) to determine the adhesion mechaninsm of metastatic human pancreatic cancer cells to ECM proteins. Methods: The expression of integrin subunits and their alteration by IL-1α were studied by flow-cytometric analysis and cellular-ELISA in metastatic human pancreatic cancer cell lines. Cancer cell adhesion to ECM proteins was assayed to determine if increased integrin expression actually affected adhesive interaction between cancer cells and putative integrin ECM ligands. Result: The α₆β₁ subunit expressed in metastatic cancer cells was enhanced by IL-1α. Metastatic cancer cells also showed preferential adherence to laminin compared to nonmetastatic cancer cells, and this was enhanced by IL-1α. Conclusions: In pancreatic cancer, the enhancement of α₆β₁-integrin by IL-1α through IL-1RI plays an important role in metastasis formation.

Key words
adhesion molecules, Interleukin-1α, metastasis, pancreatic cancer, integrin

Reprint requests
Hirozumi Sawai First Department of Surgery, Nagoya City University Medical School
1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601 JAPAN

Accepted
February 27, 2002

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