Antiangiogenic mechanisms and factors in breast cancer treatment

Castañeda-Gill, Jessica M.; Vishwanatha, Jamboor K.

doi:10.4103/1477-3163.176223

Cited by 42 publications

(14 citation statements)

References 195 publications

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“…In this case, there is a need for recruitment of new blood vessels by angiogenesis [3,4]. Tumor angiogenesis is a very complex process and can be regulated by several mechanisms involving different cell types of the tumor microenvironment that release pro-angiogenic factors such as vascular endothelial growth factor (VEGF) [5].…”

Section: Introductionmentioning

confidence: 99%

Melatonin restrains angiogenic factors in triple-negative breast cancer by targeting miR-152-3p: In vivo and in vitro studies

et al. 2018

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Section: Introductionmentioning

confidence: 99%

Melatonin restrains angiogenic factors in triple-negative breast cancer by targeting miR-152-3p: In vivo and in vitro studies

et al. 2018

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“…The architecture of the cancer vasculature is distorted with leaky and disorganized blood vessels sharing characteristics of arterioles, capillaries, and venules [ 10 ]. Variable density of contractile elements challenges interventions to substantially modify tumor perfusion.…”

Section: Introductionmentioning

confidence: 99%

Murine breast cancer feed arteries are thin-walled with reduced α1A-adrenoceptor expression and attenuated sympathetic vasocontraction

et al. 2018

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BackgroundPerfusion of breast cancer tissue limits oxygen availability and metabolism but angiogenesis inhibitors have hitherto been unsuccessful for breast cancer therapy. In order to identify abnormalities and possible therapeutic targets in mature cancer arteries, we here characterize the structure and function of cancer feed arteries and corresponding control arteries from female FVB/N mice with ErbB2-induced breast cancer.MethodsWe investigated the contractile function of breast cancer feed arteries and matched control arteries by isometric myography and evaluated membrane potentials and intracellular [Ca2+] using sharp electrodes and fluorescence microscopy, respectively. Arterial wall structure is assessed by transmission light microscopy of arteries mounted in wire myographs and by evaluation of histological sections using the unbiased stereological disector technique. We determined the expression of messenger RNA by reverse transcription and quantitative polymerase chain reaction and studied receptor expression by confocal microscopy of arteries labelled with the BODIPY-tagged α1-adrenoceptor antagonist prazosin.ResultsBreast cancer feed arteries are thin-walled and produce lower tension than control arteries of similar diameter in response to norepinephrine, thromboxane-analog U46619, endothelin-1, and depolarization with elevated [K+]. Fewer layers of similarly-sized vascular smooth muscle cells explain the reduced media thickness of breast cancer arteries. Evidenced by lower media stress, norepinephrine-induced and thromboxane-induced tension development of breast cancer arteries is reduced more than is explained by the thinner media. Conversely, media stress during stimulation with endothelin-1 and elevated [K+] is similar between breast cancer and control arteries. Correspondingly, vascular smooth muscle cell depolarizations and intracellular Ca2+ responses are attenuated in breast cancer feed arteries during norepinephrine but not during endothelin-1 stimulation. Protein expression of α1-adrenoceptors and messenger RNA levels for α1A-adrenoceptors are lower in breast cancer arteries than control arteries. Sympathetic vasocontraction elicited by electrical field stimulation is inhibited by α1-adrenoceptor blockade and reduced in breast cancer feed arteries compared to control arteries.ConclusionThinner media and lower α1-adrenoceptor expression weaken contractions of breast cancer feed arteries in response to sympathetic activity. We propose that abnormalities in breast cancer arteries can be exploited to modify tumor perfusion and thereby either starve cancer cells or facilitate drug and oxygen delivery during chemotherapy or radiotherapy.Electronic supplementary materialThe online version of this article (10.1186/s13058-018-0952-8) contains supplementary material, which is available to authorized users.

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“…We also found the integrin family of cell adhesion receptors, important to both the angiogenesis and metastatic progression of solid tumors, to be both differentially expressed and having pathways overrepresented in the gene set corresponding to the BL2 subtype ( Supplementary Table 3 ). This feature of the BL2 network produced statistical coincidence with drugs interacting with integrins, such as vitaxin and cilengitide (Figure 4 ), both of which have been investigated as anti-angiogenic agents against breast cancers [ 29 ]. The prominence of metastatic and angiogenic mechanisms is in accordance with previous findings that the BL2 subtype exhibits the lowest pCR following standard neoadjuvant chemotherapy (0%), even when correcting for multiple clinical factors [ 9 ].…”

Section: Resultsmentioning

confidence: 99%

Differential prioritization of therapies to subtypes of triple negative breast cancer using a systems medicine method

et al. 2017

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Triple negative breast cancer (TNBC) is a group of cancers whose heterogeneity and shortage of effective drug therapies has prompted efforts to divide these cancers into molecular subtypes. Our computational platform, entitled GenEx-TNBC, applies concepts in systems biology and polypharmacology to prioritize thousands of approved and experimental drugs for therapeutic potential against each molecular subtype of TNBC. Using patient-based and cell line-based gene expression data, we constructed networks to describe the biological perturbation associated with each TNBC subtype at multiple levels of biological action. These networks were analyzed for statistical coincidence with drug action networks stemming from known drug-protein targets, while accounting for the direction of disease modulation for coinciding entities. GenEx-TNBC successfully designated drugs, and drug classes, that were previously shown to be broadly effective or subtype-specific against TNBC, as well as novel agents. We further performed biological validation of the platform by testing the relative sensitivities of three cell lines, representing three distinct TNBC subtypes, to several small molecules according to the degree of predicted biological coincidence with each subtype. GenEx-TNBC is the first computational platform to associate drugs to diseases based on inverse relationships with multi-scale disease mechanisms mapped from global gene expression of a disease. This method may be useful for directing current efforts in preclinical drug development surrounding TNBC, and may offer insights into the targetable mechanisms of each TNBC subtype.

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Antiangiogenic mechanisms and factors in breast cancer treatment

Cited by 42 publications

References 195 publications

Melatonin restrains angiogenic factors in triple-negative breast cancer by targeting miR-152-3p: In vivo and in vitro studies

Melatonin restrains angiogenic factors in triple-negative breast cancer by targeting miR-152-3p: In vivo and in vitro studies

Murine breast cancer feed arteries are thin-walled with reduced α1A-adrenoceptor expression and attenuated sympathetic vasocontraction

Differential prioritization of therapies to subtypes of triple negative breast cancer using a systems medicine method

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