title: The significance of a Cripto-1 positive subpopulation of human melanoma cells exhibiting stem cell-like characteristics.
abstract: Cripto-1 (CR-1) protein function differs according to cellular or extracellular expression. In this study, we explore the significance of cell surface CR-1 expression in human melanoma cells. Cell surface CR-1-expressing human melanoma cells (CR1-CS+) were selected by fluorescence-activated cell sorting (FACS) and grown in vitro and in vivo in nude mice to study their growth characteristics. The CR1-CS+ melanoma cells were found to express increased levels of Oct4, MDR-1 and activated c-Src compared with cells lacking this subpopulation (CR1-CS-) or unsorted cells, used as control. CR1-CS+ show reduced proliferation rates and diminished spherical colony formation compared with control cells when cultured in vitro. Orthotopic injections of CR1-CS+ in nude mice formed slow growing tumors with histologic variability across different areas of the CR1-CS+ xenografts. CR-1-expressing cells from first generation CR1-CS+ tumors showed significantly increased tumor-forming rate and aggressiveness following subsequent transplants in nude mice. These data demonstrate that within a heterogeneous melanoma cell population there resides a slow proliferating, cell surface CR-1-expressing subpopulation capable of giving rise to a fast growing, aggressive progeny that may contribute to disease recurrence and progression.
authors.affiliation: Ann & Robert H. Lurie Children's Hospital of Chicago Research Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. lstrizzi@luriechildrens.org
authors.forename: Luigi
authors.initials: L
authors.lastname: Strizzi
authors.forename: Naira V
authors.initials: NV
authors.lastname: Margaryan
authors.forename: Alina
authors.initials: A
authors.lastname: Gilgur
authors.forename: Katharine M
authors.initials: KM
authors.lastname: Hardy
authors.forename: Nicola
authors.initials: N
authors.lastname: Normanno
authors.forename: David S
authors.initials: DS
authors.lastname: Salomon
authors.forename: Mary J C
authors.initials: MJ
authors.lastname: Hendrix
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C070636:TDGF1 protein, human
keywords: Cripto-1; aggressiveness; melanoma; recurrence; target; tumorigenicity