Background: Shionogi carcinoma 115 (SC115) is an androgen-dependent medullary carcinoma with a compact cell pattern. When SC115 tumors grow in androgen-depleted hosts, spindle-shaped and round cells with abundant cytoplasm develop. These cells originate from the SC115 cells (Kitamura et al., Cancer Res 1979;39:4717; Terada et al., Lab Invest 1987;57:186).
Experimental design: We investigated whether these spindle-shaped and round cells expressed mRNAs of noncollagenous connective tissue proteins, which are expressed by normal spindle-shaped cells and normal chondrocytes in developing bones. The expression and localization of osteonectin (OSN), osteopontin (OSP), matrix Gla protein (MGP), and osteocalcin (OSC) were determined by Northern blotting and in situ hybridization.
Results: No mRNA signals of these proteins were detectable in SC115 medullary carcinoma cells growing in DS mice that had been castrated but received injections of testosterone propionate. However, when the injection of TP was stopped, spindle-shaped and round cells with abundant cytoplasm developed. The former expressed OSN and OSP signals, and the latter OSN, OSP, and MGP signals.
Conclusions: Transcripts of OSN, OSP, and MGP were expressed by some SC115-derived cells during the differentiation events that occurred after androgen removal. These results provide molecular biologic evidence that a tumor of epithelial origin can progress along the connective tissue differentiation pathway.