Induction of Vasculogenic Mimicry Overrides VEGF-A Silencing and Enriches Stem-like Cancer Cells in Melanoma

Schnegg, Caroline I.; Yang, Moon Hee; Ghosh, Subrata; Hsu, Mei‐Yu

doi:10.1158/0008-5472.can-14-1855

Cited by 86 publications

(79 citation statements)

References 49 publications

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“…These data suggest that VEGF-A can stimulate characteristics associated with tumor cell plasticity essential for VM. Indeed, compelling evidence supporting this relationship shows that the induction of VM can override VEGF-A silencing and concomitantly enrich stem cell subpopulations expressing CD133 in melanoma (Schnegg et al, 2015). …”

Section: Key Signaling Pathways In Vascular Mimicrymentioning

confidence: 99%

Tumor cell vascular mimicry: Novel targeting opportunity in melanoma

Hendrix

Seftor

et al. 2016

Pharmacology & Therapeutics

134

136

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In 1999, the American Journal of Pathology published an article, entitled “Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry” by Maniotis and colleagues, which ignited a spirited debate for several years and earned the journal's distinction of a “citation classic” (Maniotis et al., 1999). Tumor cell vasculogenic mimicry (VM), also known as vascular mimicry, describes the plasticity of aggressive cancer cells forming de novo vascular networks and is associated with the malignant phenotype and poor clinical outcome. The tumor cells capable of VM share the commonality of a stem cell-like, transendothelial phenotype, which may be induced by hypoxia. Since its introduction as a novel paradigm for melanoma tumor perfusion, many studies have contributed new findings illuminating the underlying molecular pathways supporting VM in a variety of tumors, including carcinomas, sarcomas, glioblastomas, astrocytomas, and melanomas. Of special significance is the lack of effectiveness of angiogenesis inhibitors on tumor cell VM, suggesting a selective resistance by this phenotype to conventional therapy. Facilitating the functional plasticity of tumor cell VM are key proteins associated with vascular, stem cell, extracellular matrix, and hypoxia-related signaling pathways -- each deserving serious consideration as potential therapeutic targets and diagnostic indicators of the aggressive, metastatic phenotype. This review highlights seminal findings pertinent to VM, including the effects of a novel, small molecular compound, CVM-1118, currently under clinical development to target VM, and illuminates important molecular pathways involved in the suppression of this plastic, aggressive phenotype, using melanoma as a model.

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Section: Key Signaling Pathways In Vascular Mimicrymentioning

confidence: 99%

Tumor cell vascular mimicry: Novel targeting opportunity in melanoma

Hendrix

Seftor

et al. 2016

Pharmacology & Therapeutics

134

136

View full text Add to dashboard Cite

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“…It begs the question as to whether these tumors, with a relatively unaggressive clinical course, would have exhibited a vasculogenic mimicry pattern had they not been exposed to intravitreous bevacizumab. Recent evidence does suggest that melanoma cells receiving VEGF-A inhibition undergo an adaptive resistance and adopt vasculogenic mimicry patterns as an alternative tumor perfusion strategy [17]. …”

Section: Discussionmentioning

confidence: 99%

Growth of Uveal Melanoma following Intravitreal Bevacizumab

et al. 2016

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Purpose: Typically treatment of large melanomas (by Collaborative Ocular Melanoma Study criteria) is restricted to enucleation, due to size constraints for plaque brachytherapy. Because primary and metastatic uveal melanoma cells are inhibited by bevacizumab (an anti-vascular endothelial growth factor), this prospective study evaluated the impact of intravitreal bevacizumab on large uveal melanomas that were destined for enucleation. Size reduction by bevacizumab would potentially salvage these eyes by making them eligible for treatment with plaque brachytherapy. Procedures: Two patients with large uveal melanoma were each treated with one intravitreous injection of bevacizumab (1.25 mg/0.05 mL). Results: Both tumors displayed paradoxical growth 1 week following the injection, with confirmed growth 1 week later (increase from baseline of 1.1 mm in one eye and 3.1 mm in the other eye). Both eyes were enucleated and monosomy 3 and vasculogenic mimicry patterns were identified in both tumors. At 9 years follow-up, both patients were alive and metastasis free. Conclusion: These patients demonstrate that neoadjuvant intravitreous bevacizumab does not decrease the size of large uveal melanomas and may, in fact, result in their paradoxical growth. This observation supports a cautious approach in the use of intravitreous bevacizumab for uveal melanoma, particularly in the neoadjuvant setting.

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“…However, despite improving the quality of the patients' lives, nearly all patients with GBM progress, and Bevacizumab has been shown to enhance the dissemination characteristic in GBM [72]. Schnegg et al recently demonstrated that VEGF-A inhibitors promote HIF1α-mediated expansion of the CSC population in melanoma, elegantly highlighting the role of therapy adaptive resistance mechanisms driven by the therapeutic stress induced selection pressure [73]. …”

Section: The Csc Niche and Microenvironment In Disease Progressionmentioning

confidence: 99%

Cancer Stem Cells: Cellular Plasticity, Niche, and its Clinical Relevance

Lee

Hall

Ahmed

2016

J Stem Cell Res Ther

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Cancer handles an estimated 7.6 million deaths worldwide per annum. A recent theory focuses on the role Cancer Stem Cells (CSCs) in driving tumorigenesis and disease progression. This theory hypothesizes that a population of the tumor cell with similar functional and phenotypic characteristics as normal tissue stem cells are responsible for formation and advancement of many human cancers. The CSCs subpopulation can differentiate into non-CSC tumor cells and promote phenotypic and functional heterogeneity within the tumor. The presence of CSCs has been reported in a number of human cancers including blood, breast, brain, colon, lung, pancreas prostate and liver. Although the origin of CSCs remains a mystery, recent reports suggest that the phenotypic characteristics of CSCs may be plastic and are influenced by the microenvironment specific for the individual tumor. Such factors unique to each tumor preserve the dynamic balance between CSCs to non-CSCs cell fate, as well as maintain the proper equilibrium. Alternating such equilibrium via dedifferentiation can result in aggressiveness, as CSCs are considered to be more resistant to the conventional cancer treatments of chemotherapy and radiation. Understanding how the tumoral microenvironment affects the plasticity driven CSC niche will be critical for developing a more effective treatment for cancer by eliminating its aggressive and recurring nature that now is believed to be perpetuated by CSCs.

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Induction of Vasculogenic Mimicry Overrides VEGF-A Silencing and Enriches Stem-like Cancer Cells in Melanoma

Cited by 86 publications

References 49 publications

Tumor cell vascular mimicry: Novel targeting opportunity in melanoma

Tumor cell vascular mimicry: Novel targeting opportunity in melanoma

Growth of Uveal Melanoma following Intravitreal Bevacizumab

Cancer Stem Cells: Cellular Plasticity, Niche, and its Clinical Relevance

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