<Originals>ICAM-1 expression in a lymph node metastasis model of rat uterine corpus cancer in reference to metastatic activity

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To elucidate the mechanism of lymph node metastasis by tumor cells, we investigated rat Walker 256 (W256) cells with a low metastatic potential and a highly metastatic subline (PL3) that we established for sensitivity to immunocompetent cells involving ICAM-1/LFA-1-mediated cell adhesion. Immune electron microscopy revealed that cell adhesion mediated by ICAM-1/LFA-1 played a role in contact between W256 cells and lymphocytes. Immune electron microscopy also revealed that LFA-1 was expressed on the cells of marginal lymphatic sinues. These cells, forming lymphatic sinues, may be barriers to the infiltration of W256 cells with high ICAM-1 expression into the lymph nodes from sinues. Co-culture of PL3 cells with lymphocytes and co-culture of W256 cells with lymphocytes resulted in an increase in INF-γ and TNF-α in the culture solutions. The concentrations of these cytokines were found higher compared with cultures of lymph node cells alone. Flow cytometry showed that addition of IFN-γ and TNF-α increased the surface expression of ICAM-1 on W256 cells to a higher degree than on PL3 cells. In the lymph node microenvironment, cytokines may alter the surface expression of ICAM-1 on W256 and PL3 cells, and these changes may influence migration of tumor cells within the nodes and escape from immune surveillance. Such a mechanism may influence the formation of lymph node metastasis.
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