Inhibition of cancer cell motility and invasion by interleukin-12.
Tumour cell motility and attachment are crucial requirements in the formation of metastatic lesions. These properties are affected by a number of cytokines including hepatocyte growth factor/scatter factor (HGF/SF) and several immunoregulatory proteins, including interleukin-12 (IL-12). Although IL-12 has been reported to exhibit potent anti-tumour effects in vivo, a direct effect of IL-12 on cancer cells has not been reported. We show here that IL-12 directly inhibited the attachment of the human colon cancer cell lines HRT18, HT29 and HT115 to Matrigel, HGF/SF-stimulated cell motility and HGF/SF-induced cell invasion through a reconstituted basement membrane. IL-12 did not affect the growth of these cell lines. Flow cytometry, Western analysis and immunohistochemistry revealed an up-regulation of E-cadherin cell-surface adhesion molecules. These direct effects of IL-12 on colon cancer cells suggest a potentially important role for IL-12 in metastasis.
Hiscox
S
S
Department of Surgery, University of Wales College of Medicine, Cardiff, UK.
Hallett
M B
MB
Puntis
M C
MC
Jiang
W G
WG
D015153:Blotting, Western; D015820:Cadherins / Q000032:analysis; D002448:Cell Adhesion / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002462:Cell Membrane / Q000737:chemistry; D002465:Cell Movement / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D018664:Interleukin-12 / Q000494:pharmacology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D015820:Cadherins; D018664:Interleukin-12