Progression of cancer to the metastatic state involves multiple cellular and genetic changes. Using somatic cell hybridization, we demonstrated that acquisition of metastatic ability requires both the loss of metastasis suppressor functions and the activation of oncogenes. We cloned a gene, termed KAI1, that can suppress the metastatic ability of a rat prostatic cancer cell line. We found that KAI1 is highly expressed in normal prostate and breast epithelial cells but is dramatically lower in cancer cell lines derived from metastatic tumors. We also found reduced or altered protein expression in human bladder, endometrial, lung, colon, ovarian, and melanoma cancer cell lines. We are currently developing new antibody reagents that will allow study of KAI1 expression in archived tissue sections.We have collected primary and metastatic tumor specimens from prostate, colon, breast, and ovarian tumors to investigate whether KAI1 expression can be used to predict the metastatic ability of primary cancers. This is the final year for this project - continuing research will be performed at NCI.
