Identification of the messenger RNA for human cutaneous fatty acid-bindingprotein as a metastasis inducer

Using our recently developed systematic differential display and complete c omparison of gene expression approaches combined with other methods, we hav e identified a large number of mRNAs that are expressed differentially betw een benign and malignant human cells. One such mRNA that is common to prost ate and breast carcinoma cell lines encodes the human cutaneous fatty acid- binding protein (C-FABP), Northern and slot blot analyses confirm that the expression levels of C-FABP mRNA in the malignant prostate and breast carci noma cell lines are 4.9 +/- 0.9- to 16.9 +/- 2.1-fold higher than those exp ressed in the benign cell lines. A similar difference between the benign an d malignant cell lines was also detected at the protein level. In situ hybr idization experiments have detected overexpression of the mRNA for C-FABP i n human prostate carcinoma tissues. Transfection of a C-FABP expression con struct into the benign, nonmetastatic rat mammary epithelial cell line Rama 37 and inoculation of the C-FABP expression transfectants into syngeneic W istar-Furth rats produce a significant number (P < 0.05) of animals with me tastases (6 of 26 animals), whereas the control transfectants generated by the vector alone yield no such metastases, Measurements of mRNA and protein levels with Northern and Western blotting show that C-FABP is not expresse d in the control transfectant cells produced by the vector alone but is hig hly expressed in the pool of C-FABP transfectants and the sublines establis hed from their metastases, Immunocytochemical staining with antibodies to C -FABP shows that C-FABP is not expressed in the primary tumors developed fr om the control transfectants that have failed to metastasize, but it is exp ressed in both the primary tumors developed from the C-FABP transfectants a nd their metastases, Reinoculation of the sublines established from metasta ses in syngeneic rats has produced a higher proportion (50%) of animals (7 of 14 animals) with metastases than that obtained in the first-round inocul ations, indicating that the metastatic clones have been preferentially sele cted from the original pool of metastatic and nonmetastatic transfectant cl ones. These results have demonstrated that elevated expression of C-FABP ca n induce metastasis and that metastatic capability has been transferred in a genetically dominated manner in this Rama 37 model. Thus, we suggest that C-FABP is a metastasis-inducing gene, and under suitable conditions, it ma y induce metastasis of some human cancers.