The absence of a stromal protein called caveolin-1 appears to be a marker for advanced prostate cancer and for metastasis, researchers from the Kimmel Cancer Center at Jefferson and Harvard Medical School reported in “Cell Cycle.” Caveolin-1 has already been shown to be a good biomarker serving as a prognostic factor for breast cancer.
The researchers found that 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.
They also found that 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.
Dr. Lisanti, who is the director of the Jefferson Stem Cell Biology and Regenerative Medicine Center at the Kimmel Cancer Center, stated that caveolin-1 is expressed by cells in the stroma. These calls, called fibroblasts, 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.
PSA testing is unreliable, so we need better, more accurate biomarkers. We need biomarkers that can sort out which cancers have progressed or might progress from those cancers that are indolent.
Why haven’t we heard more about expanded studies looking at stromal caveolin-1 levels?
Study collaborators included 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.
Joel T Nowak, MA, MSW