The significance of a Cripto-1 positive subpopulation of human melanoma cells exhibiting stem cell-like characteristics

Luigi Strizzi, Naira V. Margaryan, Alina Gilgur, Katharine M. Hardy, Nicola Normanno, David S. Salomon, Mary J C Hendrix

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1450-1456
Number of pages7
JournalCell Cycle
Volume12
Issue number9
DOIs
Publication statusPublished - May 1 2013

Fingerprint

Melanoma
Stem Cells
Nude Mice
Neoplasms
Heterografts
Disease Progression
Cultured Cells
Flow Cytometry
Transplants
Recurrence
Injections
Growth
Population

Keywords

  • Aggressiveness
  • Cripto-1
  • Melanoma
  • Recurrence
  • Target
  • Tumorigenicity

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology
  • Medicine(all)

Cite this

Strizzi, L., Margaryan, N. V., Gilgur, A., Hardy, K. M., Normanno, N., Salomon, D. S., & Hendrix, M. J. C. (2013). The significance of a Cripto-1 positive subpopulation of human melanoma cells exhibiting stem cell-like characteristics. Cell Cycle, 12(9), 1450-1456. https://doi.org/10.4161/cc.24601

The significance of a Cripto-1 positive subpopulation of human melanoma cells exhibiting stem cell-like characteristics. / Strizzi, Luigi; Margaryan, Naira V.; Gilgur, Alina; Hardy, Katharine M.; Normanno, Nicola; Salomon, David S.; Hendrix, Mary J C.

In: Cell Cycle, Vol. 12, No. 9, 01.05.2013, p. 1450-1456.

Research output: Contribution to journalArticle

Strizzi, L, Margaryan, NV, Gilgur, A, Hardy, KM, Normanno, N, Salomon, DS & Hendrix, MJC 2013, 'The significance of a Cripto-1 positive subpopulation of human melanoma cells exhibiting stem cell-like characteristics', Cell Cycle, vol. 12, no. 9, pp. 1450-1456. https://doi.org/10.4161/cc.24601
Strizzi, Luigi ; Margaryan, Naira V. ; Gilgur, Alina ; Hardy, Katharine M. ; Normanno, Nicola ; Salomon, David S. ; Hendrix, Mary J C. / The significance of a Cripto-1 positive subpopulation of human melanoma cells exhibiting stem cell-like characteristics. In: Cell Cycle. 2013 ; Vol. 12, No. 9. pp. 1450-1456.
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