44-kd oncofetal transplantation antigen in rodent and human fetal cells. Implications of recrudescence in human and rodent cancers.

Abstract

This article summarizes the phase-specific nature of a cell surface, 44-kd tumor-associated transplantation antigen glycoprotein expressed during early and middle gestation in a portion of rodent and human fetal cells during normal fetal tissue development and illustrates how this glycoprotein is consistently recrudesced in primary and established human squamous cell carcinomas and other human and rodent tumors. The oncofetal antigen was not detectable in any human or rodent term fetal tissue or normal adult tissues tested. The tumor-associated transplantation antigen was tumor specific, yet not germ-line specific (expressed in lymphomas, sarcomas, and carcinomas) in human or rodent cancers. Rodent model tumor studies have shown 44-kd oncofetal antigen can act as a tumor-associated autoantigen of potential use in cancer detection and therapy. The oncofetal antigen was detected by immunogenicity, flow cytometry, and Western blotting in syngeneic rodent tumor recipients and by the last two methods in humans with progressive cancer. Syngeneically derived mouse monoclonal antibody (MoAb 115) was used to identify 44-kd oncofetal antigen. Early to middle gestation, oncofetal antigen-positive, mouse embryo/fetal cells used to stimulate the hybridoma were tested for immunogenicity as a tumor-associated transplantation antigen in syngeneic hosts. Patients presenting with head and neck squamous cell carcinoma (N = 25) and other carcinomas at the University of South Alabama Medical Center, Mobile, underwent a biopsy, and the tumors were mechanically dispersed and were then tested for oncofetal antigen expression directly in flow cytometry. The tumors were also cultured and tested as squamous carcinoma cell lines. Growing squamous carcinoma cells and uncultured tumor cells were stained with MoAb 115 or control MoAb. Extracts of the cells were banded by electrophoresis in gels, Western blotted, and reacted with MoAbs and enzyme-linked immunosorbent assay second antibody. Time-mated mouse fetus and human fetal cells were also stained with MoAb 115 or control antibody and analyzed in the flow cytometer. Eight- to 13-day mouse fetal cells conferred protection against syngeneic tumor challenge. Term 18- to 21-day fetal or neonate or adult mouse cells were nonprotective. All head and neck squamous cell carcinomas tested expressed 44-kd oncofetal antigen by flow cytometric analysis and in Western blots as did ATCC cell lines of these tumors, whereas normal control tissues were negative. Second trimester human fetal cells were 44-kd oncofetal antigen positive. A large spectrum of rodent sarcomas and lymphomas express the OFA. Shared 44-kd oncofetal antigen OFA offers promise as a tumor detection marker in human squamous cell carcinoma and other human carcinoma development, and syngeneic mouse tumors are good model systems to explore oncofetal antigen antigenicity.