Growth inhibition and differentiation of human salivary adenocarcinoma cells by medium conditioned with normal human fibroblasts.
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.
Shirasuna
K
K
First Department of Oral and Maxillofacial Surgery, Osaka University School of Dentistry, Japan.
Morioka
S
S
Watatani
K
K
Hayashido
Y
Y
Furusawa
H
H
Sugiyama
M
M
Okura
M
M
Matsuya
T
T
D000230:Adenocarcinoma / Q000473:pathology*; D002454:Cell Differentiation; D002455:Cell Division; D003470:Culture Media; D004247:DNA / Q000096:biosynthesis; D005347:Fibroblasts / Q000032:analysis / Q000502:physiology*; D006025:Glycosaminoglycans / Q000096:biosynthesis; D006131:Growth Inhibitors / Q000032:analysis; D006801:Humans; D012468:Salivary Gland Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
D003470:Culture Media; D006025:Glycosaminoglycans; D006131:Growth Inhibitors; D004247:DNA