Tumor angiogenesis revisited: Regulators and clinical implications

Ronca, Roberto; Benkheil, Mohammed; Mitola, Stefania; Struyf, Sofie; Liekens, Sandra

doi:10.1002/med.21452

Cited by 147 publications

(128 citation statements)

References 428 publications

(696 reference statements)

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“…Neovascularization is one of the hallmarks of cancer as it is a necessary process to provide tumor with its metabolic requirements, while simultaneously creating an escape route by which cancer cells will disseminate [1, 2]. Thus, several angiogenesis inhibitors have been developed and most of them target vascular endothelial growth factor (VEGF) signaling [3].…”

Section: Introductionmentioning

confidence: 99%

BMP9, but not BMP10, acts as a quiescence factor on tumor growth, vessel normalization and metastasis in a mouse model of breast cancer

Ouarné

Bouvard

Boneva

et al. 2018

J Exp Clin Cancer Res

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BackgroundAngiogenesis has become an attractive target for cancer therapy. However, despite the initial success of anti-VEGF (Vascular endothelial growth factor) therapies, the overall survival appears only modestly improved and resistance to therapy often develops. Other anti-angiogenic targets are thus urgently needed. The predominant expression of the type I BMP (bone morphogenetic protein) receptor ALK1 (activin receptor-like kinase 1) in endothelial cells makes it an attractive target, and phase I/II trials are currently being conducted. ALK1 binds with strong affinity to two ligands that belong to the TGF-ß family, BMP9 and BMP10. In the present work, we addressed their specific roles in tumor angiogenesis, cancer development and metastasis in a mammary cancer model.MethodsFor this, we used knockout (KO) mice for BMP9 (constitutive Gdf2-deficient), for BMP10 (inducible Bmp10-deficient) and double KO mice (Gdf2 and Bmp10) in a syngeneic immunocompetent orthotopic mouse model of spontaneous metastatic breast cancer (E0771).ResultsOur studies demonstrate a specific role for BMP9 in the E0771 mammary carcinoma model. Gdf2 deletion increased tumor growth while inhibiting vessel maturation and tumor perfusion. Gdf2 deletion also increased the number and the mean size of lung metastases. On the other hand, Bmp10 deletion did not significantly affect the E0771 mammary model and the double deletion (Gdf2 and Bmp10) did not lead to a stronger phenotype than the single Gdf2 deletion.ConclusionsAltogether, our data show that in a tumor environment BMP9 and BMP10 play different roles and thus blocking their shared receptor ALK1 is maybe not appropriate. Indeed, BMP9, but not BMP10, acts as a quiescence factor on tumor growth, lung metastasis and vessel normalization. Our results also support that activating rather than blocking the BMP9 pathway could be a new strategy for tumor vessel normalization in order to treat breast cancer.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0885-1) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

BMP9, but not BMP10, acts as a quiescence factor on tumor growth, vessel normalization and metastasis in a mouse model of breast cancer

Ouarné

Bouvard

Boneva

et al. 2018

J Exp Clin Cancer Res

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“…The net result of neovascularization is an extensive network of poorly organized tumor vessels. Tumor vessels are tortuous, often large and uneven in diameter, slow flowing, and leaky . Leakage of contrast from tumor vessels is visible as enhancement on conventional postcontrast T 1 ‐weighted MRI.…”

mentioning

confidence: 99%

Perfusion MRI in treatment evaluation of glioblastomas: Clinical relevance of current and future techniques

Dijken

Laar

Smits

et al. 2018

Magnetic Resonance Imaging

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Treatment evaluation of patients with glioblastomas is important to aid in clinical decisions. Conventional MRI with contrast is currently the standard method, but unable to differentiate tumor progression from treatment‐related effects. Pseudoprogression appears as new enhancement, and thus mimics tumor progression on conventional MRI. Contrarily, a decrease in enhancement or edema on conventional MRI during antiangiogenic treatment can be due to pseudoresponse and is not necessarily reflective of a favorable outcome. Neovascularization is a hallmark of tumor progression but not for posttherapeutic effects. Perfusion‐weighted MRI provides a plethora of additional parameters that can help to identify this neovascularization. This review shows that perfusion MRI aids to identify tumor progression, pseudoprogression, and pseudoresponse. The review provides an overview of the most applicable perfusion MRI methods and their limitations. Finally, future developments and remaining challenges of perfusion MRI in treatment evaluation in neuro‐oncology are discussed. Level of Evidence: 3 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2019;49:11–22.

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“…Accumulating evidence has demonstrated that the clinical usages of antiangiogenic and antitumor drugs are involved in toxic side effects, tumor resistance, aggressive tumor cells, and developed metastasis (Ronca, Benkheil, Mitola, Struyf, & Liekens, ). However, it is becoming increasingly obvious that natural product–based medicinal compounds and extracts can be potential therapeutics for blocking angiogenesis and tumor growth while avoiding significant side effects (Wang Dabrosin, et al., ).…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of Pectinase‐Treated Prunus Mume Fruit Concentrate on Colorectal Cancer Proliferation and Angiogenesis of Endothelial Cells

Cho

Kim

Won

et al. 2019

Journal of Food Science

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Pectinase is a well‐known enzyme used in the food processing industry to produce fruit juice and concentrate. This study evaluated the anticancer and antiangiogenesis activities of pectinase‐treated Prunus mume fruit concentrate (PC) and its phenolic components. PC treatment (250 to 1,000 µg/mL) resulted in decreased proliferation of SW480 human colorectal cancer cells through S‐phase cell cycle arrest; however, equivalent concentrations of PC did not show toxicity toward CRL‐1539 colon normal cells. Furthermore, PC‐induced caspase‐dependent apoptosis in SW480 cells, which was characterized by accumulation of apoptotic cell population, cell shrinkage, formation of apoptotic bodies, upregulation of proapoptotic Bax, cleaved PARP, caspase‐3, caspase‐8, and caspase‐9, and downregulation of antiapoptotic Bcl‐2. Antiangiogenesis effects of PC were assessed using human umbilical vein endothelial cells (HUVECs). We found that PC did not inhibit HUVECs proliferation at concentrations of 500 to 1,500 µg/mL. In addition, treatment with PC at nontoxic concentrations (500 to 1,000 µg/mL) blocked vascular endothelial growth factor induced cell migration, invasion, capillary‐like tube formation, and angiogenesis from rat aortic rings. HPLC‐PDA analysis showed that there were at least four different phenolics including 5‐HMF, neochlorogenic acid, protocatechuic acid, and syringic acid. Taken together, these results indicated that PC could be used as a good source of phenolic compounds with selective anticancer and antiangiogenesis activities. Practical Application Pectinases are one of the well‐known enzyme used in the part of food processing. Treatment of pectinase is a useful strategy to reduce viscosity, turbidity, and pulp particles in the production of fruit juice, extract, and concentrate. In the present study, we found that pectinase‐treated P. mume fruit concentrate significantly suppresses colorectal cancer proliferation and angiogenesis of human umbilical vein endothelial cells. The significance of our findings is that pectinase‐treated P. mume concentrate may be used as a commercial functional food material to inhibit colorectal cancer and angiogenesis.

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Tumor angiogenesis revisited: Regulators and clinical implications

Abstract: Since Judah Folkman hypothesized in 1971 that angiogenesis is required for solid tumor growth, numerous studies have been con-

Cited by 147 publications

References 428 publications

BMP9, but not BMP10, acts as a quiescence factor on tumor growth, vessel normalization and metastasis in a mouse model of breast cancer

BMP9, but not BMP10, acts as a quiescence factor on tumor growth, vessel normalization and metastasis in a mouse model of breast cancer

Perfusion MRI in treatment evaluation of glioblastomas: Clinical relevance of current and future techniques

Inhibitory Effects of Pectinase‐Treated Prunus Mume Fruit Concentrate on Colorectal Cancer Proliferation and Angiogenesis of Endothelial Cells

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