In the past decade significant advances in establishing the underlying biological mechanisms of tumour invasion and metastasis have been made. Some of the triggering factors and genes relevant to metastatic spread have been identified. Advances have also been made in understanding the signal transduction pathways involved in invasion and metastasis. This increased comprehension of the malignant metastatic process has enabled new antimetastatic strategies to be devised. This review summarizes progress in these areas and discusses the implications for the treatment of metastasis.

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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.

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