[Adhesion molecules and carbohydrates in cancer metastasis]

Cancer metastasis is a complex phenomenon consisting of several sequential steps: invasion of primary sites, entry into blood or lymphatic vessels, transport, lodgement, extravasation, and growth at the target sites. These steps are achieved by peculiar interactions between tumor cells and host tissues. We developed several sublines from rat ascites hepatoma AH7974 that displayed different substrates adhesiveness and lung metastatic potential and demonstrated that the expression of 62 and 56kDa laminin-like substances with alpha-galactose residues on tumor cell surfaces is one of the determinants associated with the lung-colonizing potential of these cells. So, we expanded our investigation to detect the metastasis/prognosis-related carbohydrate antigens in primary cancers of the breast, lung, stomach, and large intestine by lectin histochemistry or immunohistochemistry. The results showed that certain types of carbohydrate antigen expressions in cancer cells are profoundly related to not only the mode of metastatic spread and the organ distribution pattern of metastasis but also the prognosis of cancer patients. Lymphatic metastasis was related to the expression of mucin core type carbohydrates (Tn antigen and Tn-like antigens) in common, whereas there were no conspicuous similarities in the hematogenous metastasis-related carbohydrates among the cancers. The expressions of blood group antigens such as ABH, Lewis and MN including their precursors appeared to be strong prognostic indicators of these cancers, although the relation of these antigens to each cancer varied. These results suggest that adhesion molecules and/or carbohydrates are one of the determinants of cancer metastasis and prognosis at least in part.