Stromal Biomarker Predicts Advanced Prostate Cancer
The absence of a stromal protein called
caveolin-1 appears to be a marker for advanced prostate cancer and metastasis,
researchers from the Kimmel Cancer
Center at Jefferson and Harvard Medical School reported in Cell
Cycle.
There was an abundance of stromal
caveolin-1 in prostate tissue taken from patients with benign prostate
hypertrophy. However, the level of stromal caveolin-1 was significantly
decreased in the prostate tissue taken from patients with localized prostate
cancer. Furthermore, all tumor tissue taken from patients with metastatic
prostate cancer was completely negative for stromal caveolin-1.
The lower levels of stromal caveolin-1
also correlated with a high Gleason score, according to Michael Lisanti, M.D.,
Ph.D., professor in the departments of Cancer Biology, Medical Oncology and
Biochemistry and Molecular Biology at Jefferson Medical College of Thomas
Jefferson University. A Gleason score is one of the most important predictors of
poor clinical outcome in prostate cancer.
According to Dr. Lisanti, who is also
director of the Jefferson Stem Cell Biology and Regenerative Medicine Center at
the Kimmel Cancer Center, caveolin-1 is expressed by cells in the stroma called
fibroblasts, which are present in the connective tissue surrounding cancer
cells. When cancer cells arise, the fibroblasts stop making caveolin-1.
“We previously showed that the absence of
stromal caveolin-1 is also associated with advanced tumor stage, early
recurrence and metastasis of breast cancer,” Dr. Lisanti said. “Now we have
identified its similar prognostic value in prostate cancer. It is possible that
this biomarker may be universal, and could widely applicable as a prognostic
indicator for other cancer types as well.”
Dr. Lisanti and colleagues analyzed 97
prostate tissue samples: 30 benign prostate hypertrophy samples, 33 localized
prostate cancer samples and 34 metastatic prostate cancer samples. They used
three tissue cores from each patient tumor sample, and analyzed each core for
stromal caveolin-1 using immunohistochemistry staining.
In addition to the association with high
Gleason score and advanced cancer, stromal caveolin-1 levels were also inversely
correlated with the expression levels of epithelial caveolin-1 and epithelial
phospho-Akt. Both of these are more established markers of advanced prostate
cancer.
“These findings provide direct evidence
of collaborative interactions between the stromal tumor microenvironment and the
tumor cells themselves,” Dr. Lisanti said.
Other study collaborators include Kimmel
Cancer Center director Richard Pestell, M.D., Ph.D., and first author Dolores Di
Vizio, M.D., Ph.D., and Michael R. Freeman, Ph.D., both of Harvard Medical
School.
Media Only Contact:
Emily Shafer
Thomas Jefferson University Hospital
Phone: (215) 955-6300
Published: 6/25/2009