Interleukin-1alpha enhances integrin alpha(6)beta(1) expression and metastatic capability of human pancreatic cancer.
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.
Sawai
Hirozumi
H
Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. cb8h-swi@asahi-net.or.jp
Funahashi
Hitoshi
H
Yamamoto
Minoru
M
Okada
Yuji
Y
Hayakawa
Tetsushi
T
Tanaka
Moritsugu
M
Takeyama
Hiromitsu
H
Manabe
Tadao
T
D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D039121:Integrin alpha6beta1 / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary*; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D053573:Receptors, Interleukin-1 Type I; D014407:Tumor Cells, Cultured
D016326:Extracellular Matrix Proteins; D039121:Integrin alpha6beta1; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I