SCIENTIFIC REPORT 2004 - Sylvester Comprehensive Cancer Center

T U M O R C E L L B I O L O G Y P R O G R A M
and specific urine test (HA-HAase test; 90 percent
accuracy) for detecting bladder cancer and
monitoring its recurrence.
Dr. Lokeshwar’s research on prostate cancer
showed that immunohistochemical localization of
both HA and HAase in prostate cancer tissues is
greater than 85 percent accurate in predicting
prognoses for prostate cancer patients and are
better than CD44v6 and microvessel density.
Furthermore, both HAase and the HA-HAase
combination are independent predictors of prognosis.
Thus, use of these markers in biopsy specimens
may help clinicians make individualized
treatment decisions and improve patients’
prognoses.
In their efforts to understand the function of
tumor-derived HAase, Dr. Lokeshwar and her
colleagues purified and cloned the first tumorderived
HAase. They have demonstrated that this
tumor-derived HAase degrades tumor-associated
HA into small angiogenic fragments, which then
interact with a HA receptor, RHAMM, on endothelial
cells. The HA fragments and RHAMM
interaction on the cell surface induces signaling
events, resulting in the stimulation of endothelial
cell functions, such as proliferation through the
mitogen-activated protein kinase (MAPK) pathway.
Endothelial cell proliferation is of key importance
in tumor angiogenesis. Their recent
work using anti-sense cDNA transfection strategy
demonstrates that tumor-derived HAase is necessary
for tumor growth and muscle invasion of
bladder tumors. This is an important finding
since 60 percent of bladder cancer patients with
muscle invasive disease die within five years.
Currently, Dr. Lokeshwar’s research focuses
on three areas. First, the laboratory is comparing
the efficacy of the HA-HAase test with other
FDA-approved bladder tumor markers for monitoring
bladder cancer recurrence. Secondly, they
are testing the potential of HAase and HA-HAase
to predict prognostic potential using prostate
biopsy specimens. Thirdly, they are investigating
the functions of HAase and HA-synthase enzymes
in bladder and prostate cancer growth
and progression.
SELECTED PUBLICATIONS
2002
Lokeshwar, VB and Soloway, MS. Re: Urine
based markers of urological malignancy. Journal
of Urology 167:1406-07, 2002.
Lokeshwar, VB , Schroeder, GL, Selzer, MG,
Hautmann, SH, Posey, JT, Duncan, RC, Watson,
R, Rose, L, Markowitz, S, and Soloway, MS.
Bladder tumor markers for monitoring recurrence
and screening comparison of hyaluronic
acid-hyaluronidase and BTA-Stat tests. Cancer
95:61-72, 2002.
Ekici, S and Lokeshwar, VB . Mesane tumoru
belirleyicileri ve HA-Haase testi. Uroloji Bulteni
13:133-40, 2002.
Lokeshwar, VB , Schroeder, GL, Carey, RI,
Soloway, MS, and Iida, N. Regulation of hyaluronidase
activity by alternative mRNA splicing.
Journal of Biological Chemistry 277:33654-63,
2002.
2003
Dandekar, DS, Lokeshwar, VB , Cevallos-
Arellano, E, Soloway, MS, and Lokeshwar, BL.
An orally active Amazonian plant extract (BIRM)
inhibits prostate cancer growth and metastasis.
Cancer Chemotherapy and Pharmacology 52:59-
66, 2003.
Simon, MA, Lokeshwar, VB , and Soloway, MS.
Current bladder cancer tests: unnecessary or beneficial?
Critical Reviews in Oncology/Hematology
47:91-107, 2003.
Franzmann, EJ, Schroeder, GL, Goodwin, WJ,
Weed, DT, Fisher, P, and Lokeshwar, VB . Expression
of tumor markers hyaluronic acid and hyaluronidase
(HYAL1) in head and neck tumors.
International Journal of Cancer 106:438-45,
2003.
Posey, JT, Soloway, MS, Ekici, S, Sofer, M,
Civantos, F, Duncan, RC, and Lokeshwar, VB .
Evaluation of the prognostic potential of hyaluronic
acid and hyaluronidase (HYAL1) for prostate
cancer. Cancer Research 63:2638-44, 2003.
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UM/Sylvester Comprehensive Cancer Center Scientific Report 2004