Host-
tumor interaction is considered critical in
carcinogenesis,
tumor invasion, and
metastasis. To explore the reciprocal effects of host-
tumor interaction, we developed a system to assess the gene expression patterns of A2058 human
melanoma cells cocultured in
fibrillar collagen with HS-68 primary human fibroblasts. The gene expression pattern of the cocultured A2058 cells was only modestly affected, whereas the HS-68 fibroblast gene expression pattern was significantly altered.
Interleukin-11 and inhibitor of
DNA-binding domain-1 gene expression in the cocultured A2058 cells was down-regulated, indicative of a proinflammatory response and resistance to apoptosis, respectively. The overall pattern of up-regulated genes indicated triggering of the proinflammatory process. In addition, the
melanoma growth and migration stimulatory
chemokines CXCL1 and CXCL2 were significantly up-regulated in the cocultured fibroblasts. These results were corroborated by additional coculture experiments with the
melanoma cell lines WM-164, BLM, and SK-Mel-28 and immunohistochemistry on invasive human
melanoma sections. Taken together, these results indicate that
tumor cells cause a proinflammatory and
melanoma growth-promoting response in stromal fibroblasts. The role of
inflammation in
carcinogenesis,
tumor promotion, invasion, and
metastasis is viewed as being increasingly important and the results of these studies underscore this as well as identify certain key
proteins that are expressed as a result of the complex interactive processes in the host-tumor microenvironment.