Contact stimulation of fibroblasts for tenascin production by melanoma cells

Abstract

Tenascin, an extracellular matrix glycoprotein, is widely expressed in the stroma of almost all types of solid tumours including malignant melanomas. On the basis of its antiadhesive character, it has been supposed that tenascin accumulation facilitates tumour cell invasion and consequent metastasis formation. We aimed to investigate the mechanism by which melanoma cells can modulate the production of tenascin by host stromal cells. The expression of tenascin in cocultures of fibroblasts and five melanoma cell lines, as well as in fibroblast monocultures treated with melanoma conditioned media, was analysed by immunofluorescent staining and image analysis. Tenascin production could not be observed in control fibroblasts or in melanoma cell monocultures. Faint labelling for tenascin could be detected in fibroblast monocultures treated with melanoma cell conditioned media while a very intense staining for tenascin could be seen in melanoma cell–fibroblast cocultures. The tenascin staining in the cocultures was associated with the fibroblasts that were in close contact with melanoma cells. The level of tenascin production around the fibroblasts in different areas of the cocultures correlated well with the density of melanoma cells. Our results indicate that tenascin production of fibroblasts in the tumour stroma is directly modulated by melanoma cells mainly through cell-to-cell contact signalling.