LOSS OF THE METASTATIC PHENOTYPE IN MURINE CARCINOMA-CELLS EXPRESSINGAN ANTISENSE RNA TO THE INSULIN-LIKE GROWTH-FACTOR RECEPTOR

The ability of malignant cells to form metastases in secondary sites r emains a major obstacle to the curative treatment of cancer, Previousl y, we identified type 1 insulin like growth factor (IGF-1) as a paracr ine mitogen for highly metastatic murine carcinoma, H-59 cells, Here t he role of IGF-I and its receptor (IGF-1R) in metastasis was further i nvestigated using H-59 cells transfected with a plasmid vector express ing IGF-1R cDNA in the antisense orientation, The transfectants had a markedly reduced expression of IGF-1R and lost the ability to respond to IGF-1 in vitro, When injected in vivo, either directly into the mic rovasculature of the liver or lung (experimental metastasis) or s.c. t o allow the growth of primary local tumors (spontaneous metastasis), t hese cells did not give rise to any metastases under conditions which allowed wild-type or control transfectants to form multiple hepatic an d pulmonary metastases. The results demonstrate that the IGF-1R can pl ay a critical role in the regulation of carcinoma metastasis.