Integrin alpha 6 regulates glioblastoma stem cells.

Abstract

Cancer stem cells (CSCs) are a subpopulation of tumor cells suggested to be critical for tumor maintenance, metastasis, and therapeutic resistance. Prospective identification and targeting of CSCs are therefore priorities for the development of novel therapeutic paradigms. Although CSC enrichment has been achieved with cell surface proteins including CD133 (Prominin-1), the roles of current CSC markers in tumor maintenance remain unclear. We examined the glioblastoma stem cell (GSC) perivascular microenvironment in patient specimens to identify enrichment markers with a functional significance and identified integrin alpha6 as a candidate. Integrin alpha6 is coexpressed with conventional GSC markers and enriches for GSCs. Targeting integrin alpha6 in GSCs inhibits self-renewal, proliferation, and tumor formation capacity. Our results provide evidence that GSCs express high levels of integrin alpha6, which can serve not only as an enrichment marker but also as a promising antiglioblastoma therapy.

• Authors: Justin D Lathia, Joseph Gallagher, John M Heddleston, Jialiang Wang, Christine E Eyler, Jennifer Macswords, Qiulian Wu, Amit Vasanji, Roger E McLendon, Anita B Hjelmeland, Jeremy N Rich
• Journal: Cell stem cell (Cell Stem Cell) Vol. 6 Issue 5 Pg. 421-32 (May 07 2010) ISSN: 1875-9777 [Electronic] United States
• PMID: 20452317 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• AC133 Antigen
• Antibodies, Blocking
• Antigens, CD
• Biomarkers, Tumor
• Glycoproteins
• Integrin alpha6
• PROM1 protein, human
• Peptides
• Prom1 protein, mouse

Topics

• AC133 Antigen
• Animals
• Antibodies, Blocking (pharmacology)
• Antigens, CD (metabolism)
• Biomarkers, Tumor (metabolism)
• Cell Proliferation (drug effects)
• Gene Knockdown Techniques
• Glioblastoma (blood supply, metabolism, pathology)
• Glycoproteins (metabolism)
• Humans
• Integrin alpha6 (metabolism)
• Mice
• Mice, Inbred BALB C
• Neoplastic Stem Cells (drug effects, metabolism, pathology)
• Neovascularization, Pathologic (metabolism, pathology)
• Peptides (metabolism)
• Phenotype