Targeting Metabolism to Counteract Tumor Angiogenesis: A Review of Patent Literature

Petrillo, Sara; Tolosano, Emanuela; Munaron, Luca; Genova, Tullio

doi:10.2174/1574892813666180528105023

Cited by 11 publications

(18 citation statements)

References 26 publications

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“…The share of proliferating cancer cells increases, and metastases grow in size when new blood vessels supplying oxygen and nutrients to metastatic cancer cells are formed [ 133 ]. This is accomplished through a multistep process termed angiogenesis [ 73 , 74 ], whereby endothelial cells lining the endoluminal face of a preexisting local vessel first degrade the vessel basement membrane, and then migrate to the perivascular matrix while proliferating [ 73 , 74 ]. This gives rise to endothelial cell solid cords that will ultimately differentiate into hollow tubes, allowing blood flow [ 73 , 74 ].…”

Section: Mmp-9 Favors Tumor Cell Adaptation To the Microenvironmenmentioning

confidence: 99%

“…This is accomplished through a multistep process termed angiogenesis [ 73 , 74 ], whereby endothelial cells lining the endoluminal face of a preexisting local vessel first degrade the vessel basement membrane, and then migrate to the perivascular matrix while proliferating [ 73 , 74 ]. This gives rise to endothelial cell solid cords that will ultimately differentiate into hollow tubes, allowing blood flow [ 73 , 74 ]. These sequential events are orchestrated by a variety of growth factors, ECM-degrading enzymes and adhesion receptors [ 73 , 74 ].…”

Section: Mmp-9 Favors Tumor Cell Adaptation To the Microenvironmenmentioning

confidence: 99%

“…This gives rise to endothelial cell solid cords that will ultimately differentiate into hollow tubes, allowing blood flow [ 73 , 74 ]. These sequential events are orchestrated by a variety of growth factors, ECM-degrading enzymes and adhesion receptors [ 73 , 74 ]. Among these molecules, MMP-9 plays a prominent role in angiogenesis by cooperating with VEGF and the αvβ3 integrin ( Table 1 ) [ 11 , 73 , 74 , 134 , 135 , 136 ].…”

Section: Mmp-9 Favors Tumor Cell Adaptation To the Microenvironmenmentioning

confidence: 99%

“…These sequential events are orchestrated by a variety of growth factors, ECM-degrading enzymes and adhesion receptors [ 73 , 74 ]. Among these molecules, MMP-9 plays a prominent role in angiogenesis by cooperating with VEGF and the αvβ3 integrin ( Table 1 ) [ 11 , 73 , 74 , 134 , 135 , 136 ]. Specifically, the MMP-9 produced by metastatic tumor cells and metastasis-infiltrating neutrophils and/or macrophages breaks down the vessel basement membrane and perivascular matrix, thereby generating ECM fragments [ 11 , 20 , 26 , 27 , 28 , 29 , 92 , 134 ].…”

Section: Mmp-9 Favors Tumor Cell Adaptation To the Microenvironmenmentioning

confidence: 99%

“…The latter, in turn, trigger αvβ3-mediated endothelial cell migration ( Table 1 ) [ 135 ]. At the same time, MMP-9 retrieves ECM-bound VEGF in a soluble form which mediates endothelial cell proliferation and endothelial cords differentiation, occurring respectively in the initial and final stages of angiogenesis ( Table 1 ) [ 65 , 73 , 74 , 136 ].…”

Section: Mmp-9 Favors Tumor Cell Adaptation To the Microenvironmenmentioning

confidence: 99%

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The Impact of Matrix Metalloproteinase-9 on the Sequential Steps of the Metastatic Process

Barillari

2020

IJMS

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In industrialized countries, cancer is the second leading cause of death after cardiovascular disease. Most cancer patients die because of metastases, which consist of the self-transplantation of malignant cells in anatomical sites other than the one from where the tumor arose. Disseminated cancer cells retain the phenotypic features of the primary tumor, and display very poor differentiation indices and functional regulation. Upon arrival at the target organ, they replace preexisting, normal cells, thereby permanently compromising the patient’s health; the metastasis can, in turn, metastasize. The spread of cancer cells implies the degradation of the extracellular matrix by a variety of enzymes, among which the matrix metalloproteinase (MMP)-9 is particularly effective. This article reviews the available published literature concerning the important role that MMP-9 has in the metastatic process. Additionally, information is provided on therapeutic approaches aimed at counteracting, or even preventing, the development of metastasis via the use of MMP-9 antagonists.

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Section: Mmp-9 Favors Tumor Cell Adaptation To the Microenvironmenmentioning

confidence: 99%

Section: Mmp-9 Favors Tumor Cell Adaptation To the Microenvironmenmentioning

confidence: 99%

Section: Mmp-9 Favors Tumor Cell Adaptation To the Microenvironmenmentioning

confidence: 99%

Section: Mmp-9 Favors Tumor Cell Adaptation To the Microenvironmenmentioning

confidence: 99%

Section: Mmp-9 Favors Tumor Cell Adaptation To the Microenvironmenmentioning

confidence: 99%

See 3 more Smart Citations

The Impact of Matrix Metalloproteinase-9 on the Sequential Steps of the Metastatic Process

Barillari

2020

IJMS

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Endothelial cells require functional FLVCR1a during developmental and adult angiogenesis

et al. 2023

Self Cite

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The Feline Leukemia Virus Subgroup C Receptor 1a (FLVCR1a) is a transmembrane heme exporter essential for embryonic vascular development. However, the exact role of FLVCR1a during blood vessel development remains largely undefined. Here, we show that FLVCR1a is highly expressed in angiogenic endothelial cells (ECs) compared to quiescent ECs. Consistently, ECs lacking FLVCR1a give rise to structurally and functionally abnormal vascular networks in multiple models of developmental and pathologic angiogenesis. Firstly, zebrafish embryos without FLVCR1a displayed defective intersegmental vessels formation. Furthermore, endothelial-specific Flvcr1a targeting in mice led to a reduced radial expansion of the retinal vasculature associated to decreased EC proliferation. Moreover, Flvcr1a null retinas showed defective vascular organization and loose attachment of pericytes. Finally, adult neo-angiogenesis is severely affected in murine models of tumor angiogenesis. Tumor blood vessels lacking Flvcr1a were disorganized and dysfunctional. Collectively, our results demonstrate the critical role of FLVCR1a as a regulator of developmental and pathological angiogenesis identifying FLVCR1a as a potential therapeutic target in human diseases characterized by aberrant neovascularization.

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Identification of bioactive anti-angiogenic components targeting tumor endothelial cells in Shenmai injection using multidimensional pharmacokinetics

Zhong

Jiang

et al. 2020

Acta Pharmaceutica Sinica B

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Shenmai injection (SMI) is a well-defined herbal preparation that is widely and clinically used as an adjuvant therapy for cancer. Previously, we found that SMI synergistically enhanced the activity of chemotherapy on colorectal cancer by promoting the distribution of drugs in xenograft tumors. However, the underlying mechanisms and bioactive constituents remained unknown. In the present work, the regulatory effects of SMI on tumor vasculature were determined, and the potential anti-angiogenic components targeting tumor endothelial cells (TECs) were identified. Multidimensional pharmacokinetic profiles of ginsenosides in plasma, subcutaneous tumors, and TECs were investigated. The results showed that the concentrations of protopanaxadiol-type (PPD) ginsenosides (Rb1, Rb2/Rb3, Rc, and Rd) in both plasma and tumors, were higher than those of protopanaxatriol-type (Rg1 and Re) and oleanane-type (Ro) ginsenosides. Among PPD-type ginsenosides, Rd exhibited the greatest concentrations in tumors and TECs after repeated injection. In vivo bioactivity results showed that Rd suppressed neovascularization in tumors, normalized the structure of tumor vessels, and improved the anti-tumor effect of 5-fluorouracil (5FU) in xenograft mice. Furthermore, Rd inhibited the migration and tube formation capacity of endothelial cells in vitro . In conclusion, Rd may be an important active form to exert the anti-angiogenic effect on tumor after SMI treatment.

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Targeting Metabolism to Counteract Tumor Angiogenesis: A Review of Patent Literature

Abstract: These findings might have important implications in clinics and could be particularly relevant to patients developing resistance to traditional anti-angiogenic drugs.

Cited by 11 publications

References 26 publications

The Impact of Matrix Metalloproteinase-9 on the Sequential Steps of the Metastatic Process

The Impact of Matrix Metalloproteinase-9 on the Sequential Steps of the Metastatic Process

Endothelial cells require functional FLVCR1a during developmental and adult angiogenesis

Identification of bioactive anti-angiogenic components targeting tumor endothelial cells in Shenmai injection using multidimensional pharmacokinetics

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