Amplification of tumor inducing putative cancer stem cells (CSCs) by vitamin A/retinol from mammary tumors

Biochem Biophys Res Commun. 2013 Jul 12;436(4):625-31. doi: 10.1016/j.bbrc.2013.05.141. Epub 2013 Jun 11.

Abstract

Solid tumors contain a rare population of cancer stem cells (CSCs) that are responsible for relapse and metastasis. The existence of CSC however, remains highly controversial issue. Here we present the evidence for putative CSCs from mammary tumors amplified by vitamin A/retinol signaling. The cells exhibit mammary stem cell specific CD29(hi)/CD49f(hi)/CD24(hi) markers, resistance to radiation and chemo therapeutic agents and form highly metastatic tumors in NOD/SCID mice. The cells exhibit indefinite self renewal as cell lines. Furthermore, the cells exhibit impaired retinol metabolism and do not express enzymes that metabolize retinol into retinoic acid. Vitamin A/retinol also amplified putative CSCs from breast cancer cell lines that form highly aggressive tumors in NOD SCID mice. The studies suggest that high purity putative CSCs can be isolated from solid tumors to establish patient specific cell lines for personalized therapeutics for pre-clinical translational applications. Characterization of CSCs will allow understanding of basic cellular and molecular pathways that are deregulated, mechanisms of tumor metastasis and evasion of therapies that has direct clinical relevance.

Keywords: Mammary tumors; Metastasis; SUM159 breast cancer cell line; Tumor inducing cancer stem cells; Vitamin A/retinol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / immunology
  • Cell Line, Tumor
  • Mammary Neoplasms, Experimental / pathology*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Mice, Transgenic
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / immunology
  • Neoplastic Stem Cells / pathology
  • Vitamin A / pharmacology*

Substances

  • Antigens, CD
  • Vitamin A