title: Gene expression profiling reveals cross-talk between melanoma and fibroblasts: implications for host-tumor interactions in metastasis.
abstract: 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.
authors.affiliation: Department of Microbiology, University of Virginia, Charlottesville, Virginia 22908-0734, USA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Gallagher
authors.forename: Yongde
authors.initials: Y
authors.lastname: Bao
authors.forename: Alyson
authors.initials: A
authors.lastname: Prorock
authors.forename: Paola
authors.initials: P
authors.lastname: Zigrino
authors.forename: Roswitha
authors.initials: R
authors.lastname: Nischt
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Politi
authors.forename: Cornelia
authors.initials: C
authors.lastname: Mauch
authors.forename: Bojan
authors.initials: B
authors.lastname: Dragulev
authors.forename: Jay William
authors.initials: JW
authors.lastname: Fox
mesh_terms: D002450:Cell Communication / Q000235:genetics*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology*; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D009362:Neoplasm Metastasis; D016133:Polymerase Chain Reaction