Effects of glycosaminoglycans and extracellular matrix components on metastatic rat rhabdomyosarcoma tumor and myoblast cell proliferation

Abstract

Experiments were performed to determine the relative effects of glycosaminoglycans and extracellular matrix components alone or in association with various substrates, including extracellular matrix, on the proliferation of rat rhabdomyosarcoma (RMS) cell lines of different metastatic potential and nontumorigenic rat myoblast L6 cells. The assays used various substrates: tissue culture plastic, type I and IV collagen, fibronectin, laminin and extracellular matrix deposited by corneal endothelial cells. In control experiments, tumor cells grew faster on fibronectin and extracellular matrix than on the other substrates, and their proliferation rate was decreased slightly by laminin. Collagens were growth-inhibitory only for the highly metastatic line. The proliferation rate of L6 myoblasts was not greatly affected by the different substrates. The addition of exogenous glycosaminoglycans to the culture medium modified cell proliferation on the various substrates. Heparin inhibited the growth of all the cell lines tested, independent of the substrate. When cultured on laminin substrate the proliferation rates of the cell lines were depressed by addition of heparan sulfate to the medium, and this effect was more pronounced in the metastatic RMS lines. Chondroitin sulfate and dermatan sulfate enhanced the growth rates of the tumorigenic cells when cultured on collagen type I surfaces. Hydrocortisone, which induces myogenic differentiation, decreased the cell proliferation rates of all the cell lines tested and intensified the inhibitory effects of heparin when added simultaneously to the culture medium. The results showed that glycosaminoglycans and other matrix components can affect the proliferation rates of rhabdomyosarcoma cell lines.

Glycosaminoglycan mimetics (RGTA) modulate adult skeletal muscle satellite cell proliferation in vitro

“…These GAGs have been shown to be synthesized by several myogenic cell lines in vitro. 45, 46 They are involved in the regulation of growth factor activity and indeed, have been shown to stimulate proliferation of myoblasts of cell line 6 when added in the culture medium 47. Each of these molecules stimulated satellite cell proliferation to a maximum of 130% in the presence of 0.1 μg/mL KS (about 1 n M ) or HS (about 2 n M ), or 1 μg/mL DS (about 26 n M ), assuming that molecular masses of KS, HS, and DS are 109, 50, and 38 kDa, respectively 48…”

Effect of Total Proteoglycans on Cell Proliferation and Tumor Formation in Mice

“…In this case, an investigation of their functional activity in vitro and in vivo is facilitated due to the existence of various technical tools (specific primers, antibodies etc). Another approach is to isolate different classes of glycosaminoglycans (HS, DS, CHS, KS, HA) and investigate their influence on cell proliferation in tissue culture (Redini et al 1990;Volpi et al 1994;Nikitovic et al 2005;Nagasawa et al 1993;Maurer et al 1994). However due to a high heterogeneity of polysaccharide chains GAG even within the same PG class, very careful attention should be paid to the problem of a sameness of PG/GAG samples.…”

“…Different glycosaminoglycans were tested to evaluate their effects on proliferation of various cell lines. It was shown that heparin (He) is able to inhibit cell proliferation, while chondroitin sulfates (CS) and dermatan sulfates (DS) significantly stimulate cell growth of rhabdomyosarcoma (RMS) (Redini et al 1990) and monoblastic leukemia cell line (U-937) (Volpi et al 1994). However for osteoblastic cell lines, an inhibitory effect of CS and DS was shown (Nikitovic et al 2005).…”