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PLoS One. 2011;6(11):e27841. doi: 10.1371/journal.pone.0027841. Epub 2011 Nov 29.

Stem cell antigen-1 (sca-1) regulates mammary tumor development and cell migration.

Author information

1
Interdepartmental Program in Cell & Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America.

Abstract

BACKGROUND:

Stem cell antigen-1 (Sca-1 or Ly6A) is a glycosyl phostidylinositol (GPI)-anchored cell surface protein associated with both stem and progenitor activity, as well as tumor initiating-potential. However, at present the functional role for Sca-1 is poorly defined.

METHODOLOGY/PRINCIPAL FINDINGS:

To investigate the role of Sca-1 in mammary tumorigenesis, we used a mammary cell line derived from a MMTV-Wnt1 mouse mammary tumor that expresses high levels of endogenous Sca-1. Using shRNA knockdown, we demonstrate that Sca-1 expression controls cell proliferation during early tumor progression in mice. Functional limiting dilution transplantations into recipient mice demonstrate that repression of Sca-1 increases the population of tumor propagating cells. In scratch monolayer assays, Sca-1 enhances cell migration. In addition, knockdown of Sca-1 was shown to affect cell adhesion to a number of different extracellular matrix components. Microarray analysis indicates that repression of Sca-1 leads to changes in expression of genes involved in proliferation, cell migration, immune response and cell organization.

CONCLUSIONS/SIGNIFICANCE:

Sca-1 exerts marked effects on cellular activity and tumorgenicity both in vitro and in vivo. A better understanding of Sca-1 function may provide insight into the broader role of GPI-anchored cell surface proteins in cancer.

PMID:
22140470
PMCID:
PMC3226565
DOI:
10.1371/journal.pone.0027841
[Indexed for MEDLINE]
Free PMC Article

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