Retinoic acid-binding protein is present in metastatic murine colon tumors as well as in Lewis lung tumors and in lungs and brains of mice bearing these tumors; however, this protein is below the limits of detection in weakly-metastatic carcinomas and in normal lung, colon, or brains. These observations are interesting since they concern the possibility of measuring the binding protein levels of colon tumors in clinical specimens as biochemical markers in human malignancy. A total of thirty-three human colon tumors and related materials were analyzed for the presence of the binding protein. The interfering serum albumin, which nonspecifically binds retinoic acid, was eliminated by affinity chromatography. Of the twenty colon, cecum, and rectum tumors analyzed, 80% contained the binding protein in detectable amounts, and 20% showed nondetectable or marginally detectable amounts. Twenty-two percent of the human colon segments isolated from patients suspected for colon tumors contained the binding protein in readily detectable amounts, whereas 78% revealed nondetectable to marginally detectable amounts. The retinoic acid-binding protein of human colon tumor shared the same ligand specificity, thiol functions in ligand-binding, and sedimentation coefficient as the binding protein isolated from chick embryo skin. However, the human protein exhibited altered isoelectric pH.
Cancer 451199-1206, 1980.
ESULTS OF RESEARCH in this laboratory support R the hypothesis that retinoic acid-binding protein (RABP), which was originally detected in chick embryo kin,'^,'^ may mediate the biological function of retinoic acid in epithelial differentiati~n,'.~ in general growth,'." and in the control of tumorigene~is.~.'~ Plasma transport of retinoic acid appears to be facilitated by serum albumin.'5,1x RABP from chick embryo skin has an S,, value of 2.0,15 an isoelectric pH of 4.5, 1 1 3 1 5 and a molecular weight of 17,800." A correlation has been observed between the binding ability of retinoic acid analogs to RABP and their biological propertic:^.'^^'^^'^ The observation that RABP is localized in the nuclei of chick embryo skin and transplantable m urine tumors'" may help in understanding the molecular mechanism of retinoic acid action in genetic control. RABP has been detected in most of the retinoid responsive tissues of rat, mouse, and chick embryo.'* Relatively more of the protein is detected in the tissues From the