COEXPRESSION OF STROMELYSIN-3 AND INSULIN-LIKE-GROWTH-FACTOR-II IN TUMORS OF ECTODERMAL, MESODERMAL, AND ENDODERMAL ORIGIN - INDICATOR OF AFETAL CELL PHENOTYPE

Stromelysin-3 (ST-3) is thought to play an important role in invasion and tumor progression. We have analyzed ST-3 expression in fibroblasts with defined topographical relations to breast cancers. We demonstrat e that these fibroblasts exhibit the same distinctive pattern of messe nger ribonucleic acid (mRNA) expression that we have previously shown for insulin-hire growth factor II (IGF-II). Tumor-derived fibroblasts and skin fibroblasts produce abundant ST-3 mRNA fibroblasts from norma l breast stroma distant from the malignant tumor in the same patient e xpress considerably less ST-3 mRNA. When we analyzed ST-3 and IGF-II g ene expression in sarcomas, we found a similar pattern of coexpression . Immunohistochemical analysis of IGF-II and ST-3 protein expression i n sarcomas and breast tumors confirmed the mRNA data. ST-3 mRNA expres sion was also seen in most colon cancer cell lines, again matching rep orts of IGF-II gene expression. As the two proteins are known to play an important role during fetal growth and development, their coexpress ion 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. Th e regained ability to express such developmentally regulated proteins might, therefore, be a more general marker indicating a fetal-type phe notype of cells in a malignant tumor.