Coexpression of Stromelysin-3 and Insulin-Like Growth Factor II in Tumors of Ectodermal, Mesodermal, and Endodermal Origin: Indicator of a Fetal Cell Phenotype

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Abstract
Stromelysin-3 (ST-3) is thought to play an important role in in- vasion and tumor progression. We have analyzed ST-3 expression in fibroblasts with defined topographical relations to breast cancers. We demonstrate that these fibroblasts exhibit the same distinctive pat- tern of messenger ribonucleic acid (mRNA) expression that we have previously shown for insulin-like growth factor II (IGF-II). Tumor- derived fibroblasts and skin fibroblasts produce abundant ST-3 mRNA. Fibroblasts from normal breast stroma distant from the ma- lignant tumor in the same patient express considerably less ST-3 mRNA. When we analyzed ST-3 and IGF-II gene expression in sar- comas, we found a similar pattern of coexpression. Immunohisto- chemical analysis of IGF-II and ST-3 protein expression in sarcomas and breast tumors confirmed the mRNA data. ST-3 mRNA expression was also seen in most colon cancer cell lines, again matching reports of IGF-II gene expression. As the two proteins are known to play an important role during fetal growth and development, their coexpression in fibroblasts from malignant tumors of ectodermal (breast cancer) and mesodermal (sarcoma) origin and in epithelial cells of endodermal origin (colon cancer) implies a more primitive cellular phenotype. The regained ability to express such developmentally regulated proteins might, therefore, be a more gen- eral marker indicating a fetal-type phenotype of cells in a malignant tumor. (J Clin Endocrinol Metab 82: 1917-1922, 1997)

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