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

Abstract

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 to non-cancer supernatants. Immunohistochemistry showed that in all carcinomas, regardless of Gleason grade, a layer of CD90-positive stromal fibroblastic cells, approximately 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 plays a role 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 ∼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.

Multiple roles of CD90 in cancer

“…Accumulating evidences show that cancer stem cells along with the cancer microenvironment are responsible for cancer progression, metastasis, and drug resistance [1][2][3][4][5][6]. CD90 is a GPI-anchored cell surface protein which is involved in cell-cell and cell-matrix interaction and has been implicated in several cancers.…”

Up-regulation of Thy-1 Promotes Invasion and Metastasis of Hepatocarcinomas

“…Recently research showed its expression in thymocytes, mesenchyme stem cells, embryo haemopoietic stem cells, smooth muscle cells, and cd34+myeloma cells. Moreover, thy-1 is regarded as a tumor stem cell marker in some cancers (Chen et al, 2005;Yamazaki et al, 2009;Mercati et al, 2009;True et al, 2010). Yang et al findings suggested thy-1+/CD45+ (Donnenberg et al, 2010) hepatocarcinoma compared to thy-1-/CD45-in liver cancer possessed the ability of conspicuous neoplasia, and thy-1+/CD44+ hepatocarcinoma cells showed enhanced tendency of invasion and metastasis.…”

The proteomics in prostate cancer biomarker discovery

“…Потенциальные маркеры включают, ТОМ 2 ОБЗОРНЫЕ СТАТЬИ 23 например, beta 2 microglobulin [55][56][57], zinc alpha 2 -glycoprotein (ZAG) [58][59][60], transforming growth factor-β1 [61][62][63], interleukin 6 [64][65][66]. CD90 [67], engrailed-2 (EN2) [68], fibronеctin 1 [57] и много других раствори-мых факторов и внутриклеточных белков, вовлеченных в структурные или метаболические функции клеток.…”

“…В свободном от клеток супернатанте, созданном после дайджеста в бессывороточной питательной сре-де коллагеназной ткани РПЖ и условно нормальной ткани, полученных при хирургической резекции пред-стательной железы, идентифицированы 3 различных CD90 (Thy-1) N-гликопептида от 2 различных N-гликосайтов [67]. Метод основан на предположе-нии, что клетки остаются активными в питательной среде, продолжая реализовывать специфичные кле-точные белки.…”

“…Авторы реши-ли протестировать мочу от больных раком на наличие фрагментов CD90, которые могли встречаться, если белок реализуется из опухолевых клеток. CD90-пептид идентифицировали в моче от больных РПЖ методом ICAT-MS / MS перед простатэктомией, но не после простатэктомии, подтверждая, что CD90 секретирует-ся тканью РПЖ и может являться кандидатным био-маркером для неинвазивного теста [67]. Кроме того, используя анализ LC-SRM-MS, 7 MS / MS фрагментов определенного пептида к CD90, вариантный белок (инвентарный номер NCBI BAD92 446) идентифици-рован в дооперационных образцах.…”