title: Clonal dominance of CD133+ subset population as risk factor in tumor             progression and disease recurrence of human cutaneous melanoma.
abstract: Chemotherapeutic refractoriness of advanced cutaneous melanoma may be linked             with melanoma-initiating cells, also known as melanoma stem cells. This study             aimed to determine relative risk of clonal dominance of the CD133+ phenotype in             tissues from melanoma patients with different clinical outcomes that could be             applied to early diagnosis, prognosis or disease monitoring. Significant overexpression             of CD133 (p<0.02) was observed by immunohistochemical staining in tissues from             patients with recurrent disease versus those without disease recurrence. Relative             risk analysis between these two groups suggested that the patients with recurrence             or metastatic lesion had a greater than 2-fold overexpression of CD133. In addition,             immunodetectable CD133 corroborated with upregulation of CD133 RNA levels (14-             to 30-fold) as assessed by quantitative real-time reverse transcription-PCR (qRT-PCR)             comparison of melanoma cell lines derived from patients with poor clinical outcomes             and short overall survival (<10 months), vs. those derived from patients with             good clinical outcomes and longer overall survival (>24 months). Further, cells             derived from patients, and MACS-sorted according to their CD133 status retained             their CD133-positivity (>95%) or CD133-negativity (>95%) for more than 8             passages in culture. CD133+ cells could repopulate and form tumors (p<0.03)             in athymic NCr-nu/nu mice within 8 weeks while no tumors were observed with CD133-             phenotype (up to 200,000 cells). Taken together, the study demonstrates, for the             first time, that there exists a clonal dominance of a CD133+ population within             the hierarchy of cells in cutaneous tissues from patients that have undergone             successive progressive stages of melanoma, from primary to metastatic lesions.             CD133, thus, provides a predictive marker of disease as well as a potential therapeutic             target of high-risk melanoma.
authors.affiliation: Department of Surgical Oncology, The Maryland Melanoma Center, The Harry and Jeanette Weinberg Cancer Institute, Baltimore, MD, USA. bkumar111@hotmail.com
authors.forename: Bhuvnesh K
authors.initials: BK
authors.lastname: Sharma
authors.forename: V
authors.initials: V
authors.lastname: Manglik
authors.forename: Michael
authors.initials: M
authors.lastname: O'Connell
authors.forename: Ashani
authors.initials: A
authors.lastname: Weeraratna
authors.forename: Edward C
authors.initials: EC
authors.lastname: McCarron
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Broussard
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Divito
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Simbulan-Rosenthal
authors.forename: Dean S
authors.initials: DS
authors.lastname: Rosenthal
authors.forename: John L
authors.initials: JL
authors.lastname: Zapas
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008545:Melanoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D012008:Recurrence; D012307:Risk Factors; D012878:Skin Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D014183:Transplantation, Heterologous
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse