Integrin alpha 6 regulates glioblastoma stem cells

By J. Lathia, J. Gallagher, John M. Heddleston, Jialiang Wang, C. Eyler, Jennifer Macswords, Qiulian Wu, A. Vasanji, R. McLendon, Anita B. Hjelmeland and 1 more. Cell Stem Cell, 2010

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Summary 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. While 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 α6 as a candidate. Integrin α6 is co-expressed with conventional GSC markers and enriches for GSCs. Targeting integrin α6 in GSCs inhibits self-renewal, proliferation, and tumor formation capacity. Our results provide evidence that GSCs express high levels of integrin α6, which can not only serve as an enrichment marker but also as a promising anti-glioblastoma therapy.

Subfields: Cell Biology, Immunology and Allergy, Oncology

View Paper: https://www.semanticscholar.org/paper/be6db82f4d82c5b212ed1148e3e0e491f48dd712

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Citations in the corpus

Hematopoiesis: a human perspective. (2012, background): “Deletion of the Polycomb-group gene Bmi1 leads to a lethal anemia in mice caused by the progressive loss of proliferative capacity of HSCs and progenitors (Lessard and Sauvageau, 2003).”
Integrin Signaling in Cancer: Mechanotransduction, Stemness, Epithelial Plasticity, and Therapeutic Resistance (2019, background): “Intriguingly, the CSCs in both types of tumors express high levels of the laminin-binding α6β1 integrin, which not only facilitates adhesion to the abluminal surface of the endothelial basement membrane but also transmits self-renewal signals through FAK (Lathia et al., 2010; Schober and Fuchs, 2011”
Cancer stem cells: current status and evolving complexities. (2012, background): “In another approach, Rich and colleagues examined the perivascular microenvironment in which brain CSCs reside and identified a6-integrin as a CSC marker that was required for maintenance of CSCs in vivo (Lathia et al., 2010).”
Reconstructing and reprogramming the tumor propagating potential of glioblastoma stem-like cells (2014, neutral): “, 2010), and integrin alpha 6 (Lathia et al., 2010), the consistency of the various markers and the extent to which genetic heterogeneity contributes to observed phenotypic differences remains controversial.”
Cancer stem cells in glioblastoma (2015, background): “This inherent persistence of CSCs under hypoxic and acidic conditions as well as the preferential utilization of HIF-2α signaling compared with NSTCs and normal progenitors promote the maintenance of selfrenewal, proliferation, and survival (Li et al. 2009b).”
Oxygen in stem cell biology: a critical component of the stem cell niche. (2010, background): “This observation has gained wider acceptance, especially with the recent identification of integrin a6 (Lathia et al., 2010) and nitric oxide (NO) (Charles et al., 2010) as potent regulators of glioma CSCs. Holland and colleagues have demonstrated that endothelial nitric oxide synthase (eNOS) is…”