Prostate adenocarcinoma is the most common malignancy in the United States, with a lifetime risk of nearly 1 in 6 and an estimated annual mortality of approximately 31,500. Prostate cancer (CaP) progresses imperceptibly and is potentially curable when organ-confined. Therefore, early detection has the potential to decrease the rate of metastasis and increase disease-free survival. A noninvasive method for early detection would encourage more men to seek treatment before their CaP has metastasized to organs locally beyond the prostate. Prostate-specific antigen (PSA) is widely used as a tumor marker in diagnosing and monitoring CaP. Serum PSA level does not increase significantly until the tumor reaches a volume that exceeds 1 cc, and it is inversely related to a tumor's histologic grade. Moreover, benign prostatic hyperplasia (BPH) can falsely elevate serum PSA. This proposal introduces a potential alternative for noninvasive diagnosis of early-stage CaP. The research focus of our laboratory is tumor-associated gangliosides, unique tumor differentiation glycoantigens formed by glycosylation of the ceramide that accumulates in tumor cells. Tumor cell death may release the gangliosides into circulation, which may induce endogenous IgM antibody response. In healthy individuals, serum levels of antiganglioside IgM antibodies decline with age and remain low (titer <50) above the age of 50. However, in prostate cancer patients above 60 years of age, serum antiganglioside IgM is highly elevated, possibly due to release and sensitization of tumor gangliosides. We hypothesize that antiganglioside antibodies in the serum of patients with early-stage CaP (Tlc) may represent potential markers for localized disease.
The specific aims of this investigation are: 1. To assess the potential of anti-GD1a IgM with and without serum PSA for diagnosis of stages T1 and T2 of various Gleason grades of CaP. 2. To purify GM1b, GD1c and GD1a from PC3 and DU145 CaP cell lines and measure the antibody response to these Ggs in sera from patients with localized CaP and BPH and in sera from age-matched healthy volunteers. 3. To compare the ganglioside profile of CaP biopsy specimens with that of CaP cell lines. Our laboratory is in a unique position to undertake this investigation. We have developed, validated and established a standard operating procedure (SOP) for ELISA for anti-Gg IgM antibodies. The SOP was used in two international multicenter trials on melanoma and for screening sera of normal and healthy individuals and melanoma, sarcoma, pancreatic and colon cancer patients. An active collaboration with Pacific Urology Institute is ongoing and will continue to be a participant in this study.
| Ravindranath, Mepur H; Yesowitch, Paul; Sumobay, Cindy et al. (2007) Glycoimmunomics of human cancer: current concepts and future perspectives. Future Oncol 3:201-14 |
| Ravindranath, Mepur H; Muthugounder, Sakunthala; Hannah, Maghasi R et al. (2007) Significance of endogenous augmentation of antiganglioside IgM in cancer patients: potential tool for early detection and management of cancer therapy. Ann N Y Acad Sci 1107:212-22 |
