MECHANISMS OF CANCER GROWTH PROMOTION BY HIV-I NEUTRALIZING ANTIBODIES

Background - Certain types of cancer, including Kaposi's sarcoma, lymp homa, or cervical cancer develop with higher frequency and in more agg ressive form in Human Immunodeficiency (HIV) positive individuals, In the present studies, reactivity of MAbs anti-HIV-I gp120/gp41 with bre ast and gynecological cancer was tested. Methods - Western blotting an d immunoprecipitation with MAb anti-HIV gp120 and MAb anti-HIV-I gp41 were done with cytoplasmic and chromatin fractions isolated from breas t MCF-7 and cervical SiHa cancer cell lines, as well as from the surgi cally removed cervical, ovarian, or endometrial cancer, and mixed Mull erian tumor. Results - HIV-I like antigens were detected in breast and gynecological cancers, but not in normal tissues. I-125-MAb anti-HIV- I gp120 was internalized, translocated to the nucleus and bound to the chromatin of breast and cervical cancer cells, Intracellular uptake o f MAb anti-HIV-I gp-120 was confirmed by indirect immunofluorescence s taining, MAb anti-HIV-I gp120 (0.02-1500 ng/ml) significantly stimulat ed growth of MCF-7 breast cancer cells, Low concentrations (0.02-0.5 n g/ml)of MAb anti-HIV-I gp120 inhibited growth of SiHa cervical cancer cells, while higher concentrations (above 100 ng/ml) promoted cell pro liferation. The increased growth of breast and cervical cancer cells i n the presence of MAb anti-HIV-I gp120 paralleled 4 and 8 fold higher RNA synthesis. Conclusions - The cancer growth-promoting action of HTV -I neutralizing antibodies might represent an explanation for HIV-link ed cervical cancer.