Angiogenesis induction in breast cancer: A paracrine paradigm

Badodekar, Nilaja; Sharma, Akshita; Patil, Vikrant R; Telang, Gaurang; Sharma, Rakesh Kumar; Patil, Shankargouda; Vyas, Nishant; Somasundaram, Indumathi

doi:10.1002/cbf.3663

Cited by 33 publications

(16 citation statements)

References 115 publications

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“…Cancer cells in uence angiogenesis by secreting various agents such as growth factors, integrin, interleukins as well as MMPs. Neovascularization promotes the progression and spread of breast cancer in return [22].…”

Section: Discussionmentioning

confidence: 99%

Dihydroartemisinin Inhibits Angiogenesis in Breast Cancer via Suppressing NF-κB/MMP-2/-9 Pathway

Rao

et al. 2022

Preprint

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Purpose Dihydroartemisinin (DHA), a derivative of artemisinin that is well-known as an antimalarial drug, has been reported to have anti-tumor and anti-angiogenesis effects. However, whether and how it inhibits angiogenesis in breast cancer is poorly understood. In this study, we detected the anti-angiogenesis effect of DHA on breast cancer. Methods Firstly, we detect the anti-angiogenesis effect of DHA on breast cancer in a chick chorioallantois membrane model. Then, we collected the conditioned medium of MDA-MB-231cells used in aortic ring angiogenesis assay, and HUVECs migration and tube formation assay. Finally, we used gelatin zymography, cellular immunofluorescence assay and western blot analysis to study signaling modulators regulated by DHA in MDA-MB-231 cells. Results The results showed that angiogenesis induced by MDA-MB-231 cells was attenuated by DHA. Vessel sprout and tube-formation of vascular endothelial cells were also depressed when cultured with CM from MDA-MB-231 pretreated with DHA. What’s more, the expression, and activities of matrix metalloproteinase 2 and 9 (MMP-2/-9) in MDA-MB-231 cells were downregulated by DHA. Further studies showed that DHA downregulated the expression of p-PI3K, p-AKT, p-ERK, and p-NF-κB proteins in tumor cells. Conclusion DHA was highly efficacious in inhibiting angiogenesis induced by breast cancer cells. The downregulating of MMP-2/9 through inhibiting phosphorylation of PI3K, AKT, and ERK in tumor cells may be the key factors in the inhibitory effect of DHA on angiogenesis.

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Section: Discussionmentioning

confidence: 99%

Dihydroartemisinin Inhibits Angiogenesis in Breast Cancer via Suppressing NF-κB/MMP-2/-9 Pathway

Rao

et al. 2022

Preprint

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“…Notably, unlike normal vessels, tumor vessels are tortuous and chaotically organized, with wide gaps between endothelial cells, detached pericytes, and basal membranes that are either too thick or too thin [ 21 ]. All these features are typical of BC [ 31 ]. Importantly, BC biopsies are routinely evaluated for vessel density, which reliably predicts the risk of BC recurrence/metastasis and, thereby, BC patients’ survival rate [ 32 , 33 ].…”

Section: The Abnormal Tumor Vasculature Of Breast Cancermentioning

confidence: 99%

“…Dysregulated tumor-associated angiogenesis is orchestrated by a variety of molecular players, such as vascular endothelial growth factor (VEGF), interleukin 8 (IL-8), pleiotrophin, angiopoietin-1, angiopoietin-2, platelet-derived growth factor (PDGF), fibroblast growth factor (FGF)-2, and transforming growth factor beta-1 (TGFβ-1). Clinical studies have shown that elevated levels of these cytokines are associated with a worse prognosis of several tumor types [ 48 , 49 , 50 ] and also play a critical role in BC progression [ 31 , 51 ].…”

Section: The Abnormal Tumor Vasculature Of Breast Cancermentioning

confidence: 99%

The Combination of Immune Checkpoint Blockade with Tumor Vessel Normalization as a Promising Therapeutic Strategy for Breast Cancer: An Overview of Preclinical and Clinical Studies

Melaiu

Vanni

Portarena

et al. 2023

IJMS

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Immune checkpoint inhibitors (ICIs) have a modest clinical activity when administered as monotherapy against breast cancer (BC), the most common malignancy in women. Novel combinatorial strategies are currently being investigated to overcome resistance to ICIs and promote antitumor immune responses in a greater proportion of BC patients. Recent studies have shown that the BC abnormal vasculature is associated with immune suppression in patients, and hampers both drug delivery and immune effector cell trafficking to tumor nests. Thus, strategies directed at normalizing (i.e., at remodeling and stabilizing) the immature, abnormal tumor vessels are receiving much attention. In particular, the combination of ICIs with tumor vessel normalizing agents is thought to hold great promise for the treatment of BC patients. Indeed, a compelling body of evidence indicates that the addition of low doses of antiangiogenic drugs to ICIs substantially improves antitumor immunity. In this review, we outline the impact that the reciprocal interactions occurring between tumor angiogenesis and immune cells have on the immune evasion and clinical progression of BC. In addition, we overview preclinical and clinical studies that are presently evaluating the therapeutic effectiveness of combining ICIs with antiangiogenic drugs in BC patients.

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“…Neovascularization in angiogenesis significantly contributes to BC progression and dissemination. BC cells are able to secrete pro-angiogenic factors, such as fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), interleukins (ILs), transforming growth factor beta (TGFβ), platelet-derived growth factor (PDGF), that control the angiogenesis and metastasis since they can trigger neovascularization [131].…”

Section: Anti-angiogenic Effectsmentioning

confidence: 99%

Fucoxanthin Is a Potential Therapeutic Agent for the Treatment of Breast Cancer

Lau

Kwan

2022

Marine Drugs

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Breast cancer (BC) is one of the most common cancers diagnosed and the leading cause of cancer-related death in women. Although there are first-line treatments for BC, drug resistances and adverse events have been reported. Given the incidence of BC keeps increasing, seeking novel therapeutics is urgently needed. Fucoxanthin (Fx) is a dietary carotenoid commonly found in seaweeds and diatoms. Both in vitro and in vivo studies show that Fx and its deacetylated metabolite fucoxanthinol (Fxol) inhibit and prevent BC growth. The NF-κB signaling pathway is considered the major pathway contributing to the anti-proliferation, anti-angiogenesis and pro-apoptotic effects of Fx and Fxol. Other signaling molecules such as MAPK, MMP2/9, CYP and ROS are also involved in the anti-cancer effects by regulating the tumor microenvironment, cancer metastasis, carcinogen metabolism and oxidation. Besides, Fx also possesses anti-obesity effects by regulating UCP1 levels and lipid metabolism, which may help to reduce BC risk. More importantly, mounting evidence demonstrates that Fx overcomes drug resistance. This review aims to give an updated summary of the anti-cancer effects of Fx and summarize the underlying mechanisms of action, which will provide novel strategies for the development of Fx as an anti-cancer therapeutic agent.

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Angiogenesis induction in breast cancer: A paracrine paradigm

Cited by 33 publications

References 115 publications

Dihydroartemisinin Inhibits Angiogenesis in Breast Cancer via Suppressing NF-κB/MMP-2/-9 Pathway

Dihydroartemisinin Inhibits Angiogenesis in Breast Cancer via Suppressing NF-κB/MMP-2/-9 Pathway

The Combination of Immune Checkpoint Blockade with Tumor Vessel Normalization as a Promising Therapeutic Strategy for Breast Cancer: An Overview of Preclinical and Clinical Studies

Fucoxanthin Is a Potential Therapeutic Agent for the Treatment of Breast Cancer

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