期刊
CANCER LETTERS
卷 430, 期 -, 页码 25-33出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2018.05.014
关键词
Cancer stem cells; Biomarkers; Therapeutic target; Prostate cancer; Gene expression
类别
资金
- United States Public Health Service Grant [R01CA108512, R21CA193080, R03CA186179]
- VA Merit Award [1I01BX002494]
- Department of Defense grant [W81XWH-15-1-0558]
- Case Comprehensive Cancer Center [P30 CA43703]
The role of CD133 (Prominin-1) as a cancer stem cell marker may be useful for therapeutic approaches and prognostication in prostate cancer patients. We investigated the stem-cell-related function and biological features of a subpopulation of CD133+ cells isolated from established primary human prostate cancer cell lines. The CD133+ cells sorted from human prostate cancer 22Rv1 exhibited high clonogenic and tumorigenic capabilities, sphere forming capacity and serially reinitiated transplantable tumors in NOD-SCID mice. Gene profiling analysis of CD133 + cells showed upregulation of markers of stem cell differentiation (CD44, Oct4, SOX9 and Nanog), epithelial-to-mesenchymal transition (c-myc and BMW, osteoblastic differentiation (Runx2), and skeletal morphogenesis (BMP2), compared to side population of CD133-cells. These cells are highly malignant and resistant to gamma-radiation and chemotherapeutic drug, docetaxel. Importantly, a docetaxel-resistant subclone was more enriched in CD133 + cells with significant increase in Runx2 expression, compared to CD133-cells. Furthermore, knockdown of Runx2 in these cells resulted in differential response to chemotherapy, sensitizing them to increased cell death. These results demonstrate therapy-resistant population with stem-like features are distinct subpopulation of malignant cells that resides within parental cell lines. The molecular signature of CD133 + cells may lead to identification of novel therapeutic targets and prognostic markers in the treatment of prostate cancer.
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