Shirasuna K, Morioka S, Watatani K, Hayashido Y, Furusawa H, Sugiyama M, Okura M, Matsuya T
First Department of Oral and Maxillofacial Surgery, Osaka University School of Dentistry, Japan.
Cancer Res. 1988 May 15;48(10):2819-24.
The present study demonstrates that normal human fibroblasts (WI-38) exert a profound influence on the growth and differentiation of HSGc-C5, a clonal neoplastic epithelial cell line of human salivary gland origin. Coculture of HSGc-C5 with WI-38 resulted in a slowing of growth and an increase in glycosaminoglycan synthesis by an indirect effect involving a diffusible factor(s). Conditioned medium (CM) from WI-38 grown in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum affected HSGc-C5 as follows. The CM suppressed growth of monolayer cells; inhibited DNA synthesis; suppressed growth (decrease in size of colonies) in semisolid agar; stimulated glycosaminoglycan synthesis, induced expression of functional markers of the salivary gland, such as the secretory component, lactoferrin, and lysozyme; inhibited expression of alkaline phosphatase; and induced morphological alteration into elongated cells. These findings strongly suggest that WI-38 CM contains a factor(s) which inhibits growth and induces differentiation of HSGc-C5. The CM was also active on other human cancer cells as a growth inhibitor, but not on normal human fibroblasts. Partial purification and characterization of the factor(s) suggests that it may be a novel protein carrying both tumor inhibiting and differentiation inducing activities.
本研究表明，正常人成纤维细胞（WI-38）对HSGc-C5（一种人唾液腺来源的克隆性肿瘤上皮细胞系）的生长和分化具有深远影响。HSGc-C5与WI-38共培养导致生长减缓，并通过涉及一种或多种可扩散因子的间接作用使糖胺聚糖合成增加。在补充有10%胎牛血清的杜尔贝科改良伊格尔培养基中培养的WI-38的条件培养基（CM）对HSGc-C5有如下影响。该CM抑制单层细胞的生长；抑制DNA合成；抑制半固体琼脂中的生长（菌落大小减小）；刺激糖胺聚糖合成，诱导唾液腺功能标志物如分泌成分、乳铁蛋白和溶菌酶的表达；抑制碱性磷酸酶的表达；并诱导形态改变为细长细胞。这些发现强烈表明，WI-38 CM含有一种或多种抑制HSGc-C5生长并诱导其分化的因子。该CM作为生长抑制剂对其他人类癌细胞也有活性，但对正常人成纤维细胞无活性。对该因子的部分纯化和特性分析表明，它可能是一种兼具肿瘤抑制和分化诱导活性的新型蛋白质。
