P&S Journal: Fall 1996, Vol.16, No.3
Prostate Cancer Progression: Potential Help from a New Gene
A newly identified gene may help control the process of tumor growth and metastasis in prostate cancer, according to a study by Dr. Paul B. Fisher, professor of clinical pathology, the Chernow Research Scientist in pathology and urology, and neuro-oncology program director. Dr. Fisher and colleagues identified the gene, prostate carcinoma tumor antigen-1 (PCTA-1), which is expressed in prostatic intraepithelial neoplasia (PIN) and metastatic disease, not in benign prostatic hypertrophy (BPH) or normal prostate tissue.
"Currently, there is no way of predicting the aggressiveness of prostate cancer-if it will be helped by surgery or chemotherapy, or if it will remain indolent and not pose a threat to the patient," says Dr. Fisher. "If the expression of this gene correlates with cancers with aggressive potential, we will have a clearer understanding of how to more effectively treat patients with prostate cancer."
In the study, published in the July 9 issue of the Proceedings of the National Academy of Sciences, researchers used monoclonal antibodies to identify the PCTA-1 gene. The protein the gene produces is a member of a protein family, called galectins, that allows cancer cells to attach both to one another and to distant sites. Both processes are considered essential for a tumor to metastasize.
The techniques the researchers used to identify the gene also have potential diagnostic and therapeutic applications: Dr. Fisher and colleagues used surface epitope masking (SEM)-a patent-pending immunological subtraction procedure that identifies molecules on the surface of genetically engineered cells even if those molecules are not known in advance. As a result of this technique, the researchers were able to develop monoclonal antibodies to PCTA-1, which is expressed on the surface of prostate cancer cells. The researchers are now using the SEM technique to search for similar genes in cancers of the breast, central nervous system, colon, and lung. "Cancer cells often contain antigens on their surfaces that are either not present or are present at lower levels than in their normal cellular counterparts," says Dr. Fisher. "SEM is an efficient and selective way to find clinically relevant tumor-associated antigens-the needle in the haystack. Both the monoclonal antibodies produced by SEM and the genes encoding these molecules should prove useful for cancer diagnosis and therapy."
In addition, the researchers are testing SEM-derived monoclonal antibodies (MABs) as a potential treatment option. So far, when the MABs are added to human prostate cancer cells grown in athymic nude mice, they inhibit the growth of the cancer and disease progression. "MABs appear to stop both the tumorigenic and metastatic potential of the cancer cells, possibly by blocking sites on the surface that allow the cancer cells to grow and form emboli," says Dr. Fisher. Moreover, experiments will begin soon to test the effect of blocking PCTA-1 expression by using an antisense approach on the cancer process.