Inhibitory effect of melatonin on hypoxia-induced vasculogenic mimicry via suppressing epithelial-mesenchymal transition (EMT) in breast cancer stem cells.

Maroufi, Nazila Fathi; Amiri, Mohammad Aghazadeh; Dizaji, Babak Faraji; Vahedian, Vahid; Akbarzadeh, Maryam; Roshanravan, Neda; Haiaty, Sanya; Nouri, Mohammad; Rashidi, Mohammad-Reza

doi:10.1016/j.ejphar.2020.173282

Cited by 48 publications

(20 citation statements)

References 33 publications

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“…In addition, our results demonstrate obviously that melatonin is a hormone with important anti-cancer activity. It may probably improve breast cancer management via overcome anti-angiogenic drug resistance [260].…”

Section: Hypoxia-induced Cancer Resistancementioning

confidence: 99%

The role of hypoxia in the tumor microenvironment and development of cancer stem cell: a novel approach to developing treatment

et al. 2021

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Hypoxia is a common feature of solid tumors, and develops because of the rapid growth of the tumor that outstrips the oxygen supply, and impaired blood flow due to the formation of abnormal blood vessels supplying the tumor. It has been reported that tumor hypoxia can: activate angiogenesis, thereby enhancing invasiveness and risk of metastasis; increase survival of tumor, as well as suppress anti-tumor immunity and hamper the therapeutic response. Hypoxia mediates these effects by several potential mechanisms: altering gene expression, the activation of oncogenes, inactivation of suppressor genes, reducing genomic stability and clonal selection. We have reviewed the effects of hypoxia on tumor biology and the possible strategiesto manage the hypoxic tumor microenvironment (TME), highlighting the potential use of cancer stem cells in tumor treatment.

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Section: Hypoxia-induced Cancer Resistancementioning

confidence: 99%

The role of hypoxia in the tumor microenvironment and development of cancer stem cell: a novel approach to developing treatment

et al. 2021

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“…A growing body of evidence has demonstrated that the interaction between the tumor microenvironment (TME) and tumor cells plays a critical role in cancer development and progression (8,9). Tumor VM formation with its non-cancer cells as macrophages and fibroblasts is associated with cancer cells invasiveness and metastasis (10,11) and the interaction of the TME in VM development is not yet understood. Therefore, elucidating mechanisms through which this interaction promotes VM formation is pivotal because they can provide new therapeutic opportunities.…”

Section: Introductionmentioning

confidence: 99%

Cooperation Between Cancer and Fibroblasts in Vascular Mimicry and N2-Type Neutrophil Recruitment via Notch2–Jagged1 Interaction in Lung Cancer

Tsai

Liu

et al. 2021

Front. Oncol.

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BackgroundAngiogenesis is required for tumor development and metastasis, which is a major part in a pro-tumor microenvironment. Vascular mimicry (VM) is a process in which cancer cells, rather than endothelia, create an alternative perfusion system to support the tumor progression.ObjectivesTo validate the role of VM and to develop a strategy to inhibit angiogenesis in lung cancer.MethodsIn this study, we utilized lung cancer samples to verify the existence of VM and conducted several experimental methods to elucidate the molecular pathways.ResultsH1299 and CL1-0 lung cancer cells were unable to form capillary-like structures. VM formation was induced by cancer-associated fibroblast (CAFs) in both in vitro and in vivo experiments. Notch2–Jagged1 cell–cell contact between cancer cells and CAFs contributes to the formation of VM networks, supported by Notch intracellular domain (NICD) 2 nuclear translocation and N2ICD target gene upregulated in lung cancer cells mixed with CAFs. The polarization of tumor-promoting N2-type neutrophil was increased by VM networks consisting of CAF and cancer cells. The intravasation of cancer cells and N2-type neutrophils were increased because of the loose junctions of VM. Disruption of cancer cell–CAF connections by a γ‐secretase inhibitor enforced the anticancer effect of anti‐vascular endothelial growth factor antibodies in a mouse model.ConclusionThis study provides the first evidence that CAFs induce lung cancer to create vascular-like networks. These findings suggest a therapeutic opportunity for improving antiangiogenesis therapy in lung cancer.

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“…Breast cancer is touted as the most common mammary gland malignancy in females globally [1]. Numerous attempts have been made to decrease the breast cancer mortality rate in patients with breast cancer but it is still the main cause of mortality in developing and industrialized countries [2]. In solid tumors, the diffusion of oxygen and nutrients is critical to promote the expansion and proliferation of cancer cells [3].…”

Section: Introductionmentioning

confidence: 99%

Thymoquinone inhibited vasculogenic capacity and promoted mesenchymal-epithelial transition of human breast cancer stem cells

Haiaty

Rashidi

Akbarzadeh

et al. 2021

BMC Complement Med Ther

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Background Vasculogenic mimicry (VM) is characterized by the formation of tubular structure inside the tumor stroma. It has been shown that a small fraction of cancer cells, namely cancer stem cells (CSCs), could stimulate the development of vascular units in the tumor niche, leading to enhanced metastasis to the remote sites. This study aimed to study the inhibitory effect of phytocompound, Thymoquinone (TQ), on human breast MDA-MB-231 cell line via monitoring Wnt/PI3K signaling pathway. Methods MDA-MB-231 CSCs were incubated with different concentrations of TQ for 48 h. The viability of CSCs was determined using the MTT assay. The combination of TQ and PI3K and Wnt3a inhibitors was examined in CSCs. By using the Matrigel assay, we measured the tubulogenesis capacity. The percent of CD24− CSCs and Rhodamine 123 efflux capacity was studied using flow cytometry analysis. Protein levels of Akt, p-Akt, Wnt3a, vascular endothelial-cadherin (VE-cadherin), and matrix metalloproteinases-2 and -9 (MMP-2 and -9) were detected by western blotting. Results TQ decreased the viability of CSCs in a dose-dependent manner. The combination of TQ with PI3K and Wnt3a inhibitors reduced significantly the survival rate compared to the control group (p < 0.05). TQ could blunt the stimulatory effect of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), fibroblast growth factor (FGF) on CSCs (p < 0.05). The vasculogenic capacity of CSCs was reduced after being-exposed to TQ (p < 0.05). Western blotting revealed the decrease of CSCs metastasis by suppressing MMP-2 and -9. The protein level of VE-cadherin was also diminished in TQ-treated CSCs as compared to the control cell (p < 0.05), indicating inhibition of mesenchymal-endothelial transition (MendT). TQ could suppress Wnt3a and PI3K, which coincided with the reduction of the p-Akt/Akt ratio. TQ had the potential to decrease the number of CD24− CSCs and Rhodamine 123 efflux capacity after 48 h. Conclusion TQ could alter the vasculogenic capacity and mesenchymal-epithelial transition of human breast CSCs in vitro. Thus TQ together with anti-angiogenic therapies may be a novel therapeutic agent in the suppression of VM in breast cancer.

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Inhibitory effect of melatonin on hypoxia-induced vasculogenic mimicry via suppressing epithelial-mesenchymal transition (EMT) in breast cancer stem cells.

Cited by 48 publications

References 33 publications

The role of hypoxia in the tumor microenvironment and development of cancer stem cell: a novel approach to developing treatment

The role of hypoxia in the tumor microenvironment and development of cancer stem cell: a novel approach to developing treatment

Cooperation Between Cancer and Fibroblasts in Vascular Mimicry and N2-Type Neutrophil Recruitment via Notch2–Jagged1 Interaction in Lung Cancer

Thymoquinone inhibited vasculogenic capacity and promoted mesenchymal-epithelial transition of human breast cancer stem cells

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