Molecular signature of cancer stem cells isolated from prostate carcinoma and expression of stem markers in different Gleason grades and metastasis

Prostate cancer (PCa) is the most frequently diagnosed malignancy in men worldwide. Chemotherapy response is very poor and resistance to hormone-based treatments is frequent in advances stages. Recently, tumor-initiating cells or cancer stem cells (CSCs) have been identified in several cancers, including PCa. These cells are thought to be responsible for therapy resistance, relapse and metastasis. In the present work, enriched populations of CSCs were obtained using a mixed procedure that included differential clone-forming ability, sphere growing induction (prostatospheres) and magnetic-associated cell sorting (MACS). Also, stem marker expression was determined in PCa biopsies of different histological grades and metastasis samples. The signature for stem markers of the isolated CSCs was CD133+/CD44+/ABCG2+/ CD24-. Expression of stem markers (CD133, CD44, and ABCG2) was higher in medium Gleason biopsies than in lower and higher grades, and lymph-node and bone metastasis samples. These results suggest that the CSCs in PCa reach an important number in medium Gleason grades, when the tumor is still confined into the gland. At this stage, the surgical treatment is usually with curative intention. However, an important percentage of patients relapse after treatment. Number and signature of CSCs may be a prognosis factor for PCa recurrence.

Sindecanos: Su potencial uso diagnóstico y pronóstico en cáncer de próstata: [revisión] / Syndecans in the diagnosis and prognosis of prostate cancer: [review]

Syndecans, a family of heparan sulphate proteoglycans that are present in the cellsurface are involved in the control o fcel lproliferation, apoptosis and transfor-mation. Syndecans 1 and 2 have a central role in processes such as position control, invasion, angiogenesis and metastases ofseveral types of cáncer The expression of Syndecan 1 in epithelial cells, decreases when cells are transformed and acquire invasive properties. This decreased expression is associated to a bad prognosis. Syndecan 2, originally described in mesenchymal cells, favors cell apoptosis, increa-ses angiogenesis and controls the death of cáncer cells subjected to chemotherapy Both syndecans are present in basal and epithelial cells of prostate cancer Their lower expression is associated to more undifferentiated tumors. Disturbances in the expression and subcellular location of syndecans predict the relapse of localized tumors. Syndecans 1 and 2 can be considered tumor suppression genes and can be targetsfor new treatments. The detection of circulating fragments of these molecules could be useful for the early detection of prostate cancer.