Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor.

By S. Bao, Qiulian Wu, S. Sathornsumetee, Y. Hao, Zhizhong Li, Anita B. Hjelmeland, Q. Shi, R. McLendon, D. Bigner, Jeremy N. Rich. Cancer Research, 2006

1,367 citations recorded by the source corpus.

Malignant gliomas are highly lethal cancers dependent on angiogenesis. Critical tumor subpopulations within gliomas share characteristics with neural stem cells. We examined the potential of stem cell-like glioma cells (SCLGC) to support tumor angiogenesis. SCLGC isolated from human glioblastoma biopsy specimens and xenografts potently generated tumors when implanted into the brains of immunocompromised mice, whereas non-SCLGC tumor cells isolated from only a few tumors formed secondary tumors when xenotransplanted. Tumors derived from SCLGC were morphologically distinguishable from non-SCLGC tumor populations by widespread tumor angiogenesis, necrosis, and hemorrhage. To determine a potential molecular mechanism for SCLGC in angiogenesis, we measured the expression of a panel of angiogenic factors secreted by SCLGC. In comparison with matched non-SCLGC populations, SCLGC consistently secreted markedly elevated levels of vascular endothelial growth factor (VEGF), which were further induced by hypoxia. In an in vitro model of angiogenesis, SCLGC-conditioned medium significantly increased endothelial cell migration and tube formation compared with non-SCLGC tumor cell-conditioned medium. The proangiogenic effects of glioma SCLGC on endothelial cells were specifically abolished by the anti-VEGF neutralizing antibody bevacizumab, which is in clinical use for cancer therapy. Furthermore, bevacizumab displayed potent antiangiogenic efficacy in vivo and suppressed growth of xenografts derived from SCLGC but limited efficacy against xenografts derived from a matched non-SCLGC population. Together these data indicate that stem cell-like tumor cells can be a crucial source of key angiogenic factors in cancers and that targeting proangiogenic factors from stem cell-like tumor populations may be critical for patient therapy.

Subfields: Cancer Research, Genetics, Oncology

View Paper: https://www.semanticscholar.org/paper/75c0711067d0128c57a725c2aa5b9018ab82f206

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Citations in the corpus

Glioblastoma Stem Cells Generate Vascular Pericytes to Support Vessel Function and Tumor Growth (2013, positive): “GSCs are often located in perivascular niches and interact with ECs in a bidirectional manner (Bao et al., 2006b; Calabrese et al., 2007).”
Cancer stem cells in glioblastoma (2015, background): “Brain CSCs have subsequently been shown to be resistant to standard-of-care chemotherapy (Chen et al. 2012) and radiotherapy (Bao et al. 2006a), underscoring their role in disease progression and recurrence.”
Hypoxia-Inducible Factors Regulate Tumorigenic Capacity of Glioma Stem Cells (2009, positive): “In Vivo Tumor Formation Assays Intracranial or subcutaneous transplantation of GSCs into nude mice was performed as described in accordance with a Duke University Institutional Animal Care and Use Committee approved protocol concurrent with national regulatory standards (Bao et al., 2006a).”
The therapeutic promise of the cancer stem cell concept. (2010, background): “Indeed, despite great promise, conventional VEGF-targeted therapies have shown an unexpectedly limited survival benefit in the clinic (68), and this had led to additional studies aimed at further dissecting the effects of VEGF inhibition on primary tumor growth and tumor metastatic potential.”
Malignant astrocytic glioma: genetics, biology, and paths to treatment. (2007, background): “There is now substantial evidence for the enrichment of in vivo cancer-forming ability of CD133 + -expressing cells for GBM (Singh et al. 2004; Bao et al. 2006a; Pic-cirillo et al. 2006) and more recently in colon cancer (O’Brien et al. 2007; Ricci-Vitiani et al. 2007).”
Phase II Trial of Bevacizumab and Irinotecan in Recurrent Malignant Glioma (2007, background): “Age (y) Median (range) 49 ( 27-66 ) Gender”
Targeting cancer stem cell pathways for cancer therapy (2020, background): “[424] [425] [426] This CSC plasticity has also been demonstrated in other tumors, including neuroblastoma, renal, breast, and ovarian cancer.”
A perivascular niche for brain tumor stem cells. (2007, background): “Furthermore, very recent studies of orthotopic glioblastoma xenografts suggest that CSCs of this brain tumor secrete angiogenic factors that promote the recruitment and formation of tumor blood vessels (Bao et al., 2006).”
Making a tumour's bed: glioblastoma stem cells and the vascular niche (2007, background): “However, a series of recently published studies have shown that aberrant vascular stem cell niches, reminiscent of those observed in the normal brain, exist in glioblastoma and other types of brain tumour and support the cancer stem cell”
The brain tumor microenvironment (2011, background): “In addition, VEGF has also been shown to mediate BTSC intercellular cross-talk with tumor endothelia to induce angiogenesis (Bao et al., 2006).”
Integrin alpha 6 regulates glioblastoma stem cells (2010, methodology): “Glioblastoma stem cells (GSCs) are relatively radioresistant (Bao et al., 2006a) and chemoresistant (Liu et al., 2006).”
Hypoxia promotes expansion of the CD133-positive glioma stem cells through activation of HIF-1α (2009, background): “In that CSCs seem to have a central role in tumor initiation and recurrence, it has been suggested that definitive cancer treatment needs to target this population of cells (Reya et al., 2001; Pardal et al., 2003; Bao et al., 2006a; Vescovi et al., 2006; Park et al., 2007).”