Role of VEGFs/VEGFR-1 Signaling and Its Inhibition in Modulating Tumor Invasion: Experimental Evidence in Different Metastatic Cancer Models

Ceci, Claudia; Atzori, Maria Grazia; Lacal, Pedro Miguel; Graziani, Grazia

doi:10.3390/ijms21041388

Cited by 164 publications

(129 citation statements)

References 295 publications

(408 reference statements)

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“…CuC dual Top inhibitors display a high antiproliferative activity. Particularly, some CuC and non-CuC are dual inhibitors of Top1 and superoxide dismutase agonist [ 88 , 207 , 208 ] or Cdk receptor, like VEGF inhibitors, involved in cancer cells proliferation [ 86 , 87 , 209 , 210 ] ( Figure 5 B). Another strategy to improve therapies is the association of a CuC with a TDP1/2 (tyrosyl-DNA-phosphodiesterase 1/2) inhibitor.…”

Section: Future Strategies For Copper Complexes As Top Inhibitorsmentioning

confidence: 99%

Copper Complexes as Anticancer Agents Targeting Topoisomerases I and II

Molinaro

Martoriati

Pélinski

et al. 2020

Cancers

123

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Organometallics, such as copper compounds, are cancer chemotherapeutics used alone or in combination with other drugs. One small group of copper complexes exerts an effective inhibitory action on topoisomerases, which participate in the regulation of DNA topology. Copper complexes inhibitors of topoisomerases 1 and 2 work by different molecular mechanisms, analyzed herein. They allow genesis of DNA breaks after the formation of a ternary complex, or act in a catalytic mode, often display DNA intercalative properties and ROS production, and sometimes display dual effects. These amplified actions have repercussions on the cell cycle checkpoints and death effectors. Copper complexes of topoisomerase inhibitors are analyzed in a broader synthetic view and in the context of cancer cell mutations. Finally, new emerging treatment aspects are depicted to encourage the expansion of this family of highly active anticancer drugs and to expend their use in clinical trials and future cancer therapy.

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Section: Future Strategies For Copper Complexes As Top Inhibitorsmentioning

confidence: 99%

Copper Complexes as Anticancer Agents Targeting Topoisomerases I and II

Molinaro

Martoriati

Pélinski

et al. 2020

Cancers

123

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“…The VEGF/VEGFR-2 are important for the survival of MCF7 cells [ 56 , 57 , 58 ], but VEGFR-2 cannot be detected by Western blotting [ 59 ]. Thus, the real-time RT-PCR platform (Applied Biosystems 7500 Fast Real Time PCR System) was used to quantify the gene expression of Hsp90 and VEGFR-2 ( Table 4 ) in MCF7 cells (1 × 10 6 cells), following treatment with HAA 2020 (500, 2500, 5000 nM), dinaciclib (5, 25, 50 nM), and their combination for 24 h, as previously reported [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

Significance of Targeting VEGFR-2 and Cyclin D1 in Luminal-A Breast Cancer

et al. 2020

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The hormonal luminal-A is the most pre-dominant sub type of breast cancer (BC), and it is associated with a high level of cyclin D1 in Saudi patients. Tamoxifen is the golden therapy for hormonal BC, but resistance of cancer cells to tamoxifen contributes to the recurrence of BC due to many reasons, including high levels of AIB1 and cyclin D1. Overcoming drug resistance could be achieved by exploring alternative targetable therapeutic pathways and new drugs or combinations. The objective of this study was to determine the differentially enriched pathways in 12 samples of Saudi women diagnosed with luminal-A using the PamChip peptide microarray-based kinase activity profiling, and to compare the activity of HAA2020 and dinaciclib with tamoxifen in singles and combinations in the MCF7 luminal-A cell line. Our results of network and pathway analysis of the 12 samples highlighted the importance of VEGFR and CDKs in promoting luminal-A breast cancer. The activation of VEGF signaling via VEGFR-2 leads to activation of PI3K/AKT kinases and an increase of cell survival, and leads to activation of Hsp90, which induces the phosphorylation of FAK1, resulting in cytoskeleton remodeling. PLC-gamma 1 is also activated, leading to FAK-2 and PKC activation. Notably, the G1/S cell cycle phases and phosphorylation processes contribute to the top seven tumorigenesis processes in the 12 samples. Further, the MTT combination of HAA2020 and dinaciclib showed the best combination index (CI), was more clonogenic against MCF7 cells compared to the other combinations, and it also showed the best selectivity index (SI) in normal MRC5 cells. Interestingly, HAA2020 and dinaciclib showed a synergistic apoptotic and G1 cell cycle effect in MCF7 cells, which was supported by their synergistic CDK2, cyclin D1, and PCNA inhibition activities. Additionally, the combination showed VEGFR-2 and Hsp90 inhibition activities in MCF7 cells. The results show the significance of targeting VEGFR-2 and cyclin D1 in Saudi luminal-A breast cancer patients, and the effect of combining HAA2020 and dinaciclib on those targets in the MCF7 model. It also warrants further preclinical and in vivo investigations for the combination of HAA2020 and dinaciclib as a possible future second-line treatment for luminal-A breast cancers.

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“…These are further counted upon modifying the bioavailability of VEGF-A in the tumors by matrix metalloproteinases processing. Adding to this fact, antibody-mediated neutralization of angiopoietin 2, the ligand for the Tie2 receptor, or macrophage depletion blocks tumor angiogenesis as well as limits tumor progression in a mouse model of breast cancer [26]. Several studies conducted on the patients having cancer in liver cells showed that the marginal macrophage density is different from the macrophage density present inside the tumor of the liver although they are directly associated along with the vascular invasion, tumor multiplicity, and also fibrous capsule formation.…”

Section: Role Of Macrophage In Tumor Progressionmentioning

confidence: 99%

Role of Macrophages in Solid Tumor Metabolism

Raj¹,

Chandel²,

Maurya³

et al. 2021

Macrophages

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Cancer cells undergo several complex processes to grow and evolve. For their survival, they manipulate the entire system and acquire the ability to gain all the energy demands from the host system itself. Tumor associated macrophages (TAMs) are macrophages abundantly present in the tumor micro environment (TME) and essentially plays a critical role in coordination with the tumor cells helping them to progress and metastasize. One of the key hallmarks in tumor cells is elevated metabolic processes such as glycolysis, fatty acid oxidation, mitochondrial oxidation, and amino acid metabolism. Macrophages help cancer cells to achieve this metabolic demand through a series of signaling events including mTOR, Akt, and PI3K pathways. The M2-like phenotype of macrophages leads to the tumorous macrophage phenotype along with the tumor cells to support tumor growth through metabolic dysregulation. Focusing upon the area of macrophage-mediated tumor metabolism in solid tumors has been a new area that provides new effective targets to treat cancer. This chapter discusses the role of macrophages in tumor metabolism and cancer progression. Targeting TAMs in tumor microenvironment through metabolic axis could be a potential therapeutic option to control the solid tumor growth and propagation.

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Role of VEGFs/VEGFR-1 Signaling and Its Inhibition in Modulating Tumor Invasion: Experimental Evidence in Different Metastatic Cancer Models

Cited by 164 publications

References 295 publications

Copper Complexes as Anticancer Agents Targeting Topoisomerases I and II

Copper Complexes as Anticancer Agents Targeting Topoisomerases I and II

Significance of Targeting VEGFR-2 and Cyclin D1 in Luminal-A Breast Cancer

Role of Macrophages in Solid Tumor Metabolism

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