4.6 Article

CD90/THY1 is overexpressed in prostate cancer-associated fibroblasts and could serve as a cancer biomarker

Journal

MODERN PATHOLOGY
Volume 23, Issue 10, Pages 1346-1356

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/modpathol.2010.122

Keywords

cancer; CD90 variant; glycoproteins; prostate; proteomics; stroma; urine analysis

Categories

Funding

  1. NIH [CA111244, CA85859, P50 CA097186]
  2. Prostate Cancer Foundation
  3. NIH NCRR center [RR018522]
  4. DOE [DE-AC05-76RLO 1830]

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A by-product in the processing of prostate tissue for cell sorting by collagenase digestion is the media supernatant that remains after the cells are harvested. These supernatants contain proteins made by the cells within the tissue. Quantitative proteomic analysis of N-glycosylated proteins detected an increased amount of CD90/THY1 in cancer supernatants compared with non-cancer supernatants. Immunohistochemistry showed that in all carcinomas, regardless of Gleason grade, a layer of CD90-positive stromal fibroblastic cells, similar to 5 to 10 cells deep, was localized to tumor glands. In contrast, a no more than 1-cell wide girth of CD90-positive stromal cells was found around benign glands. The increased number of CD90-positive stromal cells in cancer correlated with overexpression of CD90 mRNA detected by gene expression analysis of stromal cells obtained by laser-capture microdissection. There is increasing evidence that cancer-associated stroma has a function in both tumor progression and carcinogenesis. Most experiments to identify cancer biomarkers have focused on the cancer cells. CD90, being a marker for prostate cancer-associated stroma, might be a potential biomarker for this cancer. A non-invasive test could be provided by a urine test. Proteomic analysis of urine from patients with prostate cancer identified CD90; conversely, CD90 was not detected in the urine of post-prostatectomy patients. Furthermore, this urinary CD90 protein was a variant CD90 protein not known to be expressed by such cells as lymphocytes that express CD90. These CD90 results were obtained from similar to 90 cases consisting of proteomic analysis of tissue and urine, immunohistochemistry, western blot analysis of tissue media, flow cytometry of cells from digested tissue, and reverse transcriptase polymerase chain reaction analysis of isolated stromal cells. Modern Pathology (2010) 23, 1346-1356; doi:10.1038/modpathol.2010.122; published online 18 June 2010

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