title: A rational approach for cancer stem-like cell isolation and characterization using CD44 and prominin-1(CD133) as selection markers.
abstract: The availability of adequate cancer stem cells or cancer stem-like cell (CSC) is important in cancer study. From ovarian cancer cell lines, SKOV3 and OVCAR3, we induced peritoneal ascites tumors in immunodeficient mice. Among the cells (SKOV3.PX1 and OVCAR3.PX1) from those tumors, we sorted both CD44 and CD133 positive cells (SKOV3.PX1_133+44+, OVCAR3.PX1_133+44+), which manifest the characteristics of self-renewal, multi-lineage differentiation, chemoresistance and tumorigenicity, those of cancer stem-like cells (CSLC). Intraperitoneal transplantation of these CD44 and CD133 positive cells resulted in poorer survival in the engrafted animals. Clinically, increased CD133 expression was found in moderately and poorly differentiated (grade II and III) ovarian serous cystadenocarcinomas. The ascites tumor cells from human ovarian cancers demonstrated more CD133 and CD44 expressions than those from primary ovarian or metastatic tumors and confer tumorigenicity in immunodeficient mice. Compared to their parental cells, the SKOV3.PX1_133+44+ and OVCAR3.PX1_133+44+ cells uniquely expressed 5 CD markers (CD97, CD104, CD107a, CD121a, and CD125). Among these markers, CD97, CD104, CD107a, and CD121a are significantly more expressed in the CD133+ and CD44+ double positive cells of human ovarian ascites tumor cells (Ascites_133+44+) than those from primary ovarian or metastatic tumors. The cancer stem-like cells were enriched from 3% to more than 70% after this manipulation. This intraperitoneal enrichment of cancer stem-like cells, from ovarian cancer cell lines or primary ovarian tumor, potentially provides an adequate amount of ovarian cancer stem-like cells for the ovarian cancer study and possibly benefits cancer therapy.
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Chief of Obstetrics and Gynecology, Tri-Service General Hospital Penghu Branch, Penghu, Taiwan.
authors.forename: Chang-Cheng
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Chief of Pathology, Da-Chien General Hospital, Miaoli, Taiwan.|Department of Rehabilitation science, Jente Junior College of Medicine, Nursing and Management, Miaoli, Taiwan.
authors.forename: Jhy-Wei
authors.initials: JW
authors.lastname: Li
authors.affiliation: Obstetrics and Gynecology, Tri-Service General Hospital, Taipei, Taiwan.
authors.forename: Chien-Chih
authors.initials: CC
authors.lastname: Ou
authors.affiliation: Medical Care and Management, Kang-Ning Junior College, Taipei, Taiwan.
authors.forename: Shih-Chung
authors.initials: SC
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Hsiu-Hsueh
authors.initials: HH
authors.lastname: Tseng
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.|Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Ming-Ching
authors.initials: MC
authors.lastname: Kao
authors.affiliation: Department of Obstetrics and Gynecology, National Defense Medical Center, Taipei, Taiwan.|Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Jah-Yao
authors.initials: JY
authors.lastname: Liu
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001202:Ascitic Fluid / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D000066673:Cell Self Renewal; D002469:Cell Separation / Q000379:methods*; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D013997:Time Factors; D047368:Tumor Burden; D014407:Tumor Cells, Cultured
chemical_list: D000071916:AC133 Antigen; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C000606023:PROM1 protein, human
keywords: CD44 and CD133; OVCAR3.PX1_133+44+; SKOV3.PX1_133+44+; cancer stem-like cells (CSLC); intraperitoneal enrichment