CANCER LETTERS ELSEVIER Cancer Letters 109 (1996) 39-47 The effect of TGF-fll on cell proliferation and proteoglycan production in human melanoma cells depends on the degree of cell differentiation Ascensih Heredia, Juan Villena, Manuel Romah, Anna Molist, Anna BassolsaT* “Departament de Bioquimica i Biologia Molecular. Facultat de Veterindria, Universitat Autonoma de Barcelona, 08193 Bellaterra, Spain Received 4 July 1996; accepted 16 July 1996 Abstract The effect of transforming growth factor fil (TGF-fil) on cell proliferation, colony formation in soft agar and synthesis and structure of proteoglycans was studied in three human melanoma cell lines at different stages of differentiation: SK-me]- 1.36- 1-5 (early), SK-mel-3.44 (intermediate) and SK-mel-23 (late). TGF-/31 potently inhibited cell growth in monolayer as well as in soft agar. TGF-fil increased the release of sulfated proteoglycans into the medium, including the cell-specific melanoma proteoglycan, mel-PG, and induced changes in disaccharide composition and sulfation of the glycosaminoglycan chains. In all the cases, the effect of TGF-@I was more pronouncedin the most undcfferentiated cell line SK-mel-1.36-1-5 than in the SK- mel-3.44, whereasit had no effect on the most differentiated SK-mel-‘23cells. Keywords: Proteoglycan; Transforming growth factor 01; Melanoma; Differentiation 1. Introduction Transforming growth factor /31-(TGF-61) is a potent growth inhibitory factor and a modulator of differentiation in several cell types. For instance, this process is promoted in chondroblasts, osteoblasts and some epithelial cells, whereas it is blocked in myoblasts, preadipocytes and lymphoid cells [ 121. Despite the relationship between TGF-/31 and cell differentiation, there are few studies dealing with the influence of the degree of cellular differentiation on TGF-0 action. Human melanoma, a highly hetero- geneous tumor, provides an interesting model in this regard since clonal cell lines derived from these * Corresponding author. Tel.: +34 3 5811042; fax: +34 3 5812006. tuma’rs provide stable and homogeneous cell popula- tions representing various degrees of differentiation [8,15]. One of the surface antigens of melanoma cells whose expression depends on the degree of cell differentiation is the melanoma-specific proteoglycan mel-.PG. Mel-PG is considered a differentiation and tumor marker since it is present in fetal but not in adult melanocytes. In tumors, it is expressed only in nevi, in the majority of malignant melanomas and in some astrocytomas and neuroblastomas [8]. Mel-PG is a chondroitin sulfate proteoglycan which consists of a 250 kDa core protein with several glicosaminoglycan (GAG) chains [4,5] and it is probably the human homologue of NG2 described in rat neural cells [ 141. On the other hand, TGF-P 1 is a potent modulator of the extracellular matrix and it is able to induce, in addition to other components, the production of sev- 0304-3835/96/$12.00 0 1996 Elsevier Science Ireland Ltd. All rights reserved PI1 SO304-3835(96)04402-3