Acquisition of tumorigenic potential and therapeutic resistance in CD133+ subpopulation of prostate cancer cells exhibiting stem-cell like characteristics. (28th August 2018)

• Record Type: Journal Article
• Authors: Kanwal, Rajnee; Shukla, Sanjeev; Walker, Ethan; Gupta, Sanjay
• Is Part Of: Cancer letters. Volume 430(2018)
• Page Start: 25
• Page End: 33
• Publication Date: 2018-08-28
• Subjects: Cancer stem cells -- Biomarkers -- Therapeutic target -- Prostate cancer -- Gene expression; ALDH1 Aldehyde Dehydrogenase 1 -- BMP2 Bone Morphogenetic Protein 2 -- CD133 Prominin-1 -- c-Myc MYC Proto-Oncogene -- CICs cancer initiating cells -- CSC cancer stem cell -- CXCR4 C-X-C Motif Chemokine Receptor 4 -- DTX Docetaxel -- Oct4 Octamer-binding transcription factor 4/POU5F1 -- FACS Fluorescence-activated cell sorting -- Runx2 Runt Related Transcription Factor 2 -- SOX2 SRY-Box 2 -- SOX-9 SRY (Sex-Determining Region Y)-Box 9 Protein; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2018.05.014
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: 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 BMI1), osteoblastic differentiation (Runx2), and skeletal morphogenesis (BMP2), compared to side population of CD133- cells. These cells are highly malignant and resistant to γ-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. Highlights: CD133+ cells possess self-renewal and sphere forming capabilities. CD133+ cells are highly tumorigenic, compared to CD133- cells. CD133+ cells are highly therapy resistant, compared to CD133- cells. CD133+ cells demonstrate stem-cell properties in prostate cancer.