Responses to paracrine chemotactic and autocrine chemokinetic factors and lung metastatic capability of mouse RAW117 large-cell lymphoma cells.

We studied the cell migration properties of poorly metastatic murine RAW117-P large-cell lymphoma cells, a highly lung metastatic subline (RAW117-L17) and a highly liver metastatic subline (RAW117-H10). L17 cells responded to the serum-free conditioned medium (CM) of mouse lung microvessel endothelial cells (MLEs) and mouse lung fibroblasts (MLFs). The migration of L17 cells was also stimulated by its own CM and, to a lesser extent, by the CM of parental (P) and H10 cells. RAW117-P and -H10 cells responded poorly to all of the CM tested. Chequerboard analyses revealed that the migration-stimulating activities of MLE CM and MLF CM were mainly chemotactic, whereas those of L17, P and H10 CM were chemokinetic. We also analysed the effect of MLE CM and MLF CM in combination with L17, P or H10 CM on cell migration of the RAW117 sublines. The migration of lung metastatic subline L17 cells to MLE or MLF CM was enhanced when L17 CM was also present. This enhancement effect was not seen when P or H10 cells were exposed to MLE or MLF CM plus the CM from P or H10 cells respectively. Thus we found that the chemotactic response of lung metastatic large-cell lymphoma cells to paracrine migration stimulation factors from lung endothelial cells and fibroblasts in concert with an autocrine chemokinetic factor may be involved in RAW117 lung-specific invasion and metastasis.