Molecular and Cellular Regulators of Cancer Angiogenesis

Goh, Pauline; Sze, Daniel Man-Yuen; Roufogalis, Basil D.

doi:10.2174/156800907783220462

Cited by 65 publications

(38 citation statements)

References 177 publications

(259 reference statements)

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“…The activation of angiogenesis is a critical step in cancer development (8), involving several kinds of stimulation, such as hypoxia, cytokines, and growth factors (7,(9)(10). Hypoxiainducible factor-1α (HIF-1α) is a pivotal transcription factor that regulates angiogenesis by inducing the expression of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), and basic fibroblast growth factor (bFGF; ref.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-519c Suppresses Hypoxia-Inducible Factor-1α Expression and Tumor Angiogenesis

Ting

Chen²,

Johansson³

et al. 2010

Cancer Research

186

113

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Hypoxia-inducible factor-1α (HIF-1α) is widely considered to be one of the key regulators of tumor angiogenesis. The upstream regulation is complex and involves several growth factors, cytokines, and hypoxia. Herein, we have identified miR-519c as a hypoxia-independent regulator of HIF-1α, acting through direct binding to the HIF-1α 3′ untranslated region and leading to reduced tumor angiogenesis. Overexpression of miR-519c resulted in a significant decrease of HIF-1α protein levels and reduced the tube formation of human umbilical vein endothelial cells; similarly, antagomir inhibition of miR-519c increased the level of HIF-1α protein and enhanced angiogenic activity, suggesting an important role of miR-519c in HIF-1α-mediated angiogenesis. Consistent with the overexpression of miR-519c in cancer patients with better prognosis, mice injected with miR-519c-overexpressing cells exhibited dramatically reduced HIF-1α levels, followed by suppressed tumor angiogenesis, growth, and metastasis. In addition, we found that hepatocyte growth factor (HGF), a known HIF-1α inducer, reduced the miR-519c levels through an Akt-dependent pathway. This regulation was posttranscriptional and may be mediated by suppression of miR-519c maturation. Taken together, our findings provide the first evidence that miR-519c is a pivotal regulator of tumor angiogenesis and that microenvironmental HGF contributes to regulating miR-519c biogenesis in cancer cells. Cancer Res; 70(7); 2675-85. ©2010 AACR.

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Section: Introductionmentioning

confidence: 99%

MicroRNA-519c Suppresses Hypoxia-Inducible Factor-1α Expression and Tumor Angiogenesis

Ting

Chen²,

Johansson³

et al. 2010

Cancer Research

186

113

View full text Add to dashboard Cite

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“…It is one of the most crucial components of the TME in promoting tumor growth, invasion, and metastasis. Studies indicated that CAFs produce and secrete many growth factors and cytokines such as TGF-β, hepatocyte growth factor (HGF), and fibroblast secreted protein-1 (FSP1) to support primary tumor growth [40,41]. CAFs can also promote angiogenesis by secreting stromal derived factor1 (SDF-1) to recruit endothelial cell precursors (EPCs) [41].…”

Section: Cellular Components In the Tme That Suppress Tumor Progressionmentioning

confidence: 99%

“…Studies indicated that CAFs produce and secrete many growth factors and cytokines such as TGF-β, hepatocyte growth factor (HGF), and fibroblast secreted protein-1 (FSP1) to support primary tumor growth [40,41]. CAFs can also promote angiogenesis by secreting stromal derived factor1 (SDF-1) to recruit endothelial cell precursors (EPCs) [41]. Interestingly, SDF-1α (also known as CXCL12) binds to CXCR4 in tumors cells to directly stimulate cancer cell proliferation [42].…”

Section: Cellular Components In the Tme That Suppress Tumor Progressionmentioning

confidence: 99%

Complex interplay between tumor microenvironment and cancer therapy

Shen

Kang

2018

Front. Med.

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Tumor microenvironment (TME) is comprised of cellular and non-cellular components that exist within and around the tumor mass. The TME is highly dynamic and its importance in different stages of cancer progression has been well recognized. A growing body of evidence suggests that TME also plays pivotal roles in cancer treatment responses. TME is significantly remodeled upon cancer therapies, and such change either enhances the responses or induces drug resistance. Given the importance of TME in tumor progression and therapy resistance, strategies that remodel TME to improve therapeutic responses are under developing. In this review, we provide an overview of the essential components in TME and the remodeling of TME in response to anti-cancer treatments. We also summarize the strategies that aim to enhance therapeutic efficacy by modulating TME.

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“…So far more than a dozen proangiogenic molecules have been reported to play an important role in tumor angiogenesis [Bouck et al, 1996;Cockerill et al, 1995;Folkman, 1995Folkman, , 1997. In addition to its predominant role in the vascular compartment, the combination of stromal cells and the microenvironment around the tumor niche may lead to the development of a variety of cancers [Barcellos-Hoff and Ravani, 2000;Bhowmick et al, 2004;Coussens and Werb, 2002;Cunha et al, 2003;Goh et al, 2007;Olumi et al, 1999]. Although the list of molecular and cellular players involved in regulation of tumor blood vessel formation is growing, we will focus and highlight only the major players.…”

Section: Molecular and Cellular Players Of Tumor Angiogenesismentioning

confidence: 99%

Targeting tumor vascular endothelium: an emerging concept for cancer therapy

Mohanraj¹,

Karumanchi²,

Sukhatme³

2008

Drug Development Research

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Although traditional chemotherapeutic agents have saved thousands of lives over the years and delayed tumor progression, they have limited efficacy due to toxicity and lack of tumor cell selectivity. Recently some of the more promising anticancer therapy approaches tested and proven in clinical studies have used a combinatorial approach of using new molecularly targeted agents with standard therapies. In this regard, inhibition of angiogenesis represents a new approach to cancer therapy. To date, many antiangiogenic agents have been developed and are in different stages of clinical development. Targeting tumor cell-associated endothelial cells may represent a potential powerful adjunct to traditional cancer therapy. In this review, we provide an overview of different approaches involved in discovery and development of anti-angiogenic agents and discuss the clinical impact of these agents. Finally, we present and summarize some of the emerging concepts such as resistance to anti-angiogenic drugs, antiangiogenic therapy-related toxicity, and integrated treatment modalities. Drug Dev Res 69 : 340-351, 2008.

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Molecular and Cellular Regulators of Cancer Angiogenesis

Cited by 65 publications

References 177 publications

MicroRNA-519c Suppresses Hypoxia-Inducible Factor-1α Expression and Tumor Angiogenesis

MicroRNA-519c Suppresses Hypoxia-Inducible Factor-1α Expression and Tumor Angiogenesis

Complex interplay between tumor microenvironment and cancer therapy

Targeting tumor vascular endothelium: an emerging concept for cancer therapy

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