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Melanoma, a tumor based on a mutant stem cell?

Publication ,  Journal Article
Grichnik, JM; Burch, JA; Schulteis, RD; Shan, S; Liu, J; Darrow, TL; Vervaert, CE; Seigler, HF
Published in: J Invest Dermatol
January 2006

Stem cells play a critical role in normal tissue maintenance, and mutations in these stem cells may give rise to cancer. We hypothesize that melanoma develops from a mutated stem cell and therefore residual stem cell characteristics should be able to be identified in melanoma cell lines. We studied three metastatic melanoma cell lines that exhibited multiple morphologic forms in culture and demonstrated the capacity to pigment. We used the ability to efflux Hoechst 33342 dye, a technique known to enrich for stem cells in many tissues, to segregate cell populations. The cells with the greatest ability to efflux the dye were (1) small in size, (2) had the capacity to give rise to larger cell forms, and (3) had the greatest ability to expand in culture. The small cells were found to have a decreased proliferative rate and were less melanized. Large dendritic cells that appeared to be nonproliferative were identified in cultures. Treatment with cytosine beta-D-arabinofuranoside hydrochloride (Ara-C) expanded the large cell population but the residual proliferative capacity, both in vitro and in vivo, remained concentrated in the smaller cell fraction. Antigenic staining patterns were variable and heterogeneous. Nestin (a neural stem cell marker) and gp100 (premelanosomal marker) favored the smaller cell population, while nerve growth factor receptor often labeled larger cells. Morphologic and antigenic heterogeneity remained intact after clonal purification. These findings are consistent with the behavior expected for a tumor based on stem cell biology; this finding has diagnostic and therapeutic implications for melanocytic neoplasias.

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Published In

J Invest Dermatol

DOI

ISSN

0022-202X

Publication Date

January 2006

Volume

126

Issue

1

Start / End Page

142 / 153

Location

United States

Related Subject Headings

  • gp100 Melanoma Antigen
  • Skin Neoplasms
  • Nestin
  • Nerve Tissue Proteins
  • Neoplastic Stem Cells
  • Neoplasm Proteins
  • Neoplasm Metastasis
  • Mutation
  • Membrane Glycoproteins
  • Melanoma
 

Citation

APA
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Grichnik, J. M., Burch, J. A., Schulteis, R. D., Shan, S., Liu, J., Darrow, T. L., … Seigler, H. F. (2006). Melanoma, a tumor based on a mutant stem cell? J Invest Dermatol, 126(1), 142–153. https://doi.org/10.1038/sj.jid.5700017
Grichnik, James M., James A. Burch, Ryan D. Schulteis, Siqing Shan, Jie Liu, Timothy L. Darrow, Carol E. Vervaert, and Hilliard F. Seigler. “Melanoma, a tumor based on a mutant stem cell?J Invest Dermatol 126, no. 1 (January 2006): 142–53. https://doi.org/10.1038/sj.jid.5700017.
Grichnik JM, Burch JA, Schulteis RD, Shan S, Liu J, Darrow TL, et al. Melanoma, a tumor based on a mutant stem cell? J Invest Dermatol. 2006 Jan;126(1):142–53.
Grichnik, James M., et al. “Melanoma, a tumor based on a mutant stem cell?J Invest Dermatol, vol. 126, no. 1, Jan. 2006, pp. 142–53. Pubmed, doi:10.1038/sj.jid.5700017.
Grichnik JM, Burch JA, Schulteis RD, Shan S, Liu J, Darrow TL, Vervaert CE, Seigler HF. Melanoma, a tumor based on a mutant stem cell? J Invest Dermatol. 2006 Jan;126(1):142–153.
Journal cover image

Published In

J Invest Dermatol

DOI

ISSN

0022-202X

Publication Date

January 2006

Volume

126

Issue

1

Start / End Page

142 / 153

Location

United States

Related Subject Headings

  • gp100 Melanoma Antigen
  • Skin Neoplasms
  • Nestin
  • Nerve Tissue Proteins
  • Neoplastic Stem Cells
  • Neoplasm Proteins
  • Neoplasm Metastasis
  • Mutation
  • Membrane Glycoproteins
  • Melanoma