Modulation of proteoglycan metabolism by hydrocortisone and by growth factors in rhabdomyosarcoma cell lines of different metastatic potentials

Abstract

Glycosaminoglycans of cultured nickel-induced rat rhabdomyosarcoma cell lines with different metastatic potentials, grown in the presence or in the absence of hydrocortisone and of growth factor (EDF and EDGF) were investigated comparatively. The newly formed [35S]sulphate and [3H]glucosamine-labelled glycosaminoglycans were analysed in the extra-, peri- and intra-cellular compartments of the following cell lines: the strongly metastatic and colonizing 9-4/0 parental line, the very weakly metastatic and weakly colonizing subline 8 and the very weakly metastatic but colonizing subline 13a2. The cell surface of the weakly metastatic 8 and 13a2 lines was richer at least 5 and 2 times respectively in sulphated glycosaminoglycan label than the surface of the strongly metastatic 9-4/0 parental line. Hydrocortisone provoked an approximately four-fold increase in the label of the sulphated cell surface glycosaminoglycans of the 9-4/0 line. The pattern of the labelled cell surface glycosaminoglycans of these cells become similar to that of cells from the very weakly invading subline 8. Hydrocortisone induced only minor changes in the distribution of the glycosaminoglycans in the 8 and 13a2 lines, and at the same time, their proliferation rate and differentiation state was only slightly affected by this drug. Conversely to hydrocortisone, EGF increases the proliferation of the 9-4/0 line and also increases the label in sulphated cell surface glycosaminoglycans. This increase is about 50 per cent of that obtained by hydrocortisone. Thus, the accumulation of the glycosaminoglycan label on the cell surface is not directly related to the cell growth in the case of these cells. The results suggest that sulphated cell surface glycosaminoglycans, especially chondroitin sulphate, are involved in the inhibition of metastasis formation of the rhabdomyosarcoma cell lines studied.