Sylvester Comprehensive Cancer Center

Vinata B. Lokeshwar, Ph.D.

Vinata B. Lokeshwar, Ph.D.

Professor of Urology

Description of Research

The major focus of Dr. Vinata Lokeshwar’s laboratory is on understanding the mechanisms of bladder, kidney and prostate cancer progression; specifically, to identify diagnostic and prognostic tumor markers which are molecular determinants of cancer progression and can be targeted for therapy and chemoprevention. For a number of years, the laboratory has been investigating how hyaluronic acid (HA), a glycosaminoglycan, and hyaluronidase (HAase), an enzyme that degrades HA, promote cancer growth, metastasis and angiogenesis. Our laboratory was one of the first to connect HAase to cancer biology and the first to identify HYAL-1 as the tumor-derived HAase. Numerous publications from our laboratory have demonstrated that the HA-family of molecules are highly accurate urine and/or tissue markers for bladder cancer detection and for predicting metastasis and survival in bladder, renal cell and prostate cancer patients. Our recent work also demonstrates that a chemokine receptor CXCR7, and its ligand stroma-derived factor-1 (SDF1)-β, are potentially accurate markers for predicting metastasis and survival in bladder and renal cell carcinomas. Taking these clinical observations back to the laboratory, we discovered that sulfated hyaluronic acid (sHA) is a relatively specific inhibitor of HYAL-1 and has potent antitumor activity in prostate cancer models. The mechanism of the antitumor activity of sHA involves inhibition of the tumor-associated HA-HAase system. We have also shown that tumor-associated HA synthesis is a target for treatment and chemoprevention. 4-methylumbelliferone (4-MU), a HA-synthesis inhibitor, is a dietary supplement consumed for improving liver health. We have demonstrated that 4-MU inhibits prostate cancer growth, invasion and angiogenesis in pre-clinical models by inhibiting HA synthesis. In a transgenic mouse prostate cancer model (TRAMP), that mimics prostate cancer progression in men, stage-specific 4-MU treatment regimens resulted in complete inhibition of tumor formation and metastasis. Further, 4-MU treatment was chemopreventive. A 4-MU (Hymecromone) based combination, developed in our laboratory, was found to abrogate kidney cancer growth and progression in pre-clinical models. The key reason why our laboratory is able to conduct translational research is the collaborations with clinicians and researchers within our university and beyond.

Highlights

  • HA-family targeted therapy for chemoprevention and treatment for bladder, kidney and prostate carcinomas.
  • HA-family and chemokine family of molecules as diagnostic and prognostic markers for bladder, kidney and prostate carcinomas.






Selected Cancer-Related Publications

  • Hautmann S, Lokeshwar VB, Juenemann KP. [Urine-based diagnostics : An update on the Kiel Tumor Bank.] Urologe A 48:619-24, 2009. Read more »
  • Shirodkar SP, Lokeshwar VB. Potential new urinary markers in the early detection of bladder cancer. Curr Opin Urol 19:488-493,2009. Read more »
  • Gomez CS, Gomez P, Knapp J, Jorda M, Soloway MS, Lokeshwar VB. Hyaluronic Acid and HYAL-1 in Prostate Biopsy Specimens: Predictors of Biochemical Recurrence. J Urol 182:1350-6,2009. Read more »

Programs

Collaborating in the Multidisciplinary Research Program(s):

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