Stromal Biomarker Predicts Advanced Prostate Cancer

29
Jun

The same biomarker was previously identified as a prognostic factor for breast 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.

Dr. Michael Lisanti

Dr. Michael Lisanti

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.