title: Melanocyte mediated paracrine induction of extracellular matrix degrading proteases in squamous cell carcinoma cells.
abstract: The expression of extracellular-matrix (ECM)-degrading proteases has been shown to be necessary for invasion of tumor cells into surrounding tissue. For several tumor types, overexpression of these proteases is dependent upon interactions with adjacent fibroblast cell populations. We previously demonstrated activation of matrix metalloprotease (MMP) and urokinase-type plasminogen activator (uPa) expression in a coculture model consisting of squamous cell carcinoma cells (SCC) with dermal fibroblasts. In the present study we have examined whether melanocytes, which are known to interact closely with keratinocytes of the basal epidermal layer, might influence ECM-degrading protease expression in SCC cells as well. Upon coculture of the human SCC cell line II-4 with the nontumorigenic mouse melanocyte cell line Melan-a or treatment of II-4 cells with Melan-a conditioned media, induction of expression of the MMP matrilysin and uPa was observed. In contrast, no induction was observed for stromelysin-1 or 92-kDa type IV collagenase. Matrilysin/uPa-inducing activity was found to act at the level of gene transcription for both matrilysin and uPa and was ubiquitously expressed among six different human melanocytic cell strains/lines, ranging from primary normal melanocytes to cell lines established from metastatic melanoma lesions. These data demonstrate that melanocytic cells can exert a paracrine influence in SCC cells on the expression of specific proteases involved in ECM turnover and tumor invasiveness.
authors.affiliation: Department of Radiation Oncology, University of Arizona Medical Center, Tucson, Arizona, 85724, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Borchers
authors.forename: L A
authors.initials: LA
authors.lastname: Sanders
authors.forename: M B
authors.initials: MB
authors.lastname: Powell
authors.forename: G T
authors.initials: GT
authors.lastname: Bowden
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000201:enzymology*; D002460:Cell Line; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D004790:Enzyme Induction; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D020783:Matrix Metalloproteinase 7; D008544:Melanocytes / Q000166:cytology / Q000502:physiology*; D008545:Melanoma; D008666:Metalloendopeptidases / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D014568:Urokinase-Type Plasminogen Activator; D008666:Metalloendopeptidases; D020783:Matrix Metalloproteinase 7