MICAL2 is expressed in cancer associated neo-angiogenic capillary endothelia and it is required for endothelial cell viability, motility and VEGF response

Barravecchia, Ivana; Mariotti, Sara; Pucci, Angela; Scebba, Francesca; Cesari, Chiara De; Bicciato, Silvio; Tagliafico, Enrico; Tenedini, Elena; Vindigni, Carla; Cecchini, Marco; Berti, Gabriele; Vitiello, Marianna; Poliseno, Laura; Mazzanti, Chiara Maria; Angeloni, Debora

doi:10.1016/j.bbadis.2019.04.008

Cited by 16 publications

(20 citation statements)

References 32 publications

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“…These factors are closely associated with the growth of tumors and angiogenesis (18,19). VEGF induces proliferation of endothelial cells in vitro, and stimulates chemotaxis of endothelial cell angiogenesis (20,21). bFGF promotes endothelial cell proliferation, stimulates chemotaxis of endo-thelial cells towards tumor tissues and upregulates production of a variety of proteases.…”

Section: Discussionmentioning

confidence: 99%

Tanshinone IIA reduces secretion of pro‑angiogenic factors and inhibits angiogenesis in human colorectal cancer

et al. 2020

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Tumor angiogenesis is an important factor which precipitates recurrence and metastasis of colorectal cancer (CRC). Angiogenesis is also a significant feature which accompanies invasion and metastasis of CRC. Tumor hypoxia activates hypoxia inducible factor (HIF), which promotes angiogenesis in CRC. HIF significantly promotes cell proliferation and angiogenesis in CRC, facilitating invasion and metastasis. Tanshinone IIA (Tan IIA) has been revealed to effectively inhibit angiogenesis in CRC, although the underlying mechanism remains to be determined. The aim of the present study was to determine the effects of HIF-1α on hypoxia induced angiogenesis in CRC cells, the effects of Tan IIA on the expression of pro-angiogenic factors in CRC cells, and on human umbilical vein endothelial cell (HUVEC) tube formation in normal and hypoxic conditions. The results of the present study revealed that Tan IIA not only decreased HIF-1α expression and inhibited the secretion level of vascular endothelial growth factor and basic fibroblast growth factor, but also efficiently decreased proliferation, tube formation and metastasis of HUVECs. The results highlight the potential of Tan IIA-mediated targeting of HIF-1α as a potential therapeutic option for treatment of patients with CRC.

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Section: Discussionmentioning

confidence: 99%

Tanshinone IIA reduces secretion of pro‑angiogenic factors and inhibits angiogenesis in human colorectal cancer

et al. 2020

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“…However, it is upregulated in only tumor-associated neoangiogenic capillaries and not in normal endothelium within the tumor in GBM human tissue samples. The inhibition of MICAL2-abolished TNF-α activation and VEGF stimulation and tumor-associated endothelial cell function [74]. Thus, there are niche-specific effects on cancer hallmark activity that may be key as the field seeks to understand how these different hallmarks can propagate cancer despite targeted therapy and treatment [75] To highlight this, Talasila et al recently proposed that angiogenesis and invasion of tumor cells occur in different niches correlative to different metabolic mechanisms.…”

Section: Angiogenesismentioning

confidence: 99%

Modulating Microenvironments for Treating Glioblastoma

Roberts

Munson

2020

Curr. Tissue Microenviron. Rep.

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Purpose of Review This review focuses on the development and progression of glioblastoma through the brain and glioma microenvironment. Specifically, we highlight how the tumor microenvironment contributes to the hallmarks of cancer in hopes of offering novel therapeutic options and tools to target. Recent Findings The hallmarks of cancer represent elements of cancer that contribute to the disease's malignancy, yet elements within the brain tumor microenvironment, such as other cellular types as well as biochemical and biophysical cues that can each uniquely affect tumor cells, have not been well-described in this context and serve as potential targets for modulation. Summary Here, we highlight how the brain tumor microenvironment contributes to the progression and therapeutic response of tumor cells. Specifically, we examine these contributions through the lens of Hanahan and Weinberg's "Hallmarks of Cancer" in order to identify potential novel targets within the brain that may offer a means to treat brain cancers, including the deadliest form of brain cancer, glioblastoma.

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“…Nowadays, drugs targeting these mechanisms are called migrastatics [12] and are particularly sought after by pharmaceutical industries. Further, we also reported that MICAL2 is expressed in neo-angiogenic endothelial cells (ECs) in human solid tumors (gastric, kidney and breast carcinoma, glioblastoma, and cardiac myxoma), and in animal models of ischemia/inflammation neo-angiogenesis, but not in the normal capillary bed [13]. Specifically, through immunohistochemistry, the expression of the MICAL2 protein was highlighted in ECs of neo-angiogenic capillaries branching off within the tumor mass of gastric, kidney, and breast carcinoma, glioblastoma, and cardiac myxoma [13].…”

Section: Introductionmentioning

confidence: 99%

“…Further, we also reported that MICAL2 is expressed in neo-angiogenic endothelial cells (ECs) in human solid tumors (gastric, kidney and breast carcinoma, glioblastoma, and cardiac myxoma), and in animal models of ischemia/inflammation neo-angiogenesis, but not in the normal capillary bed [13]. Specifically, through immunohistochemistry, the expression of the MICAL2 protein was highlighted in ECs of neo-angiogenic capillaries branching off within the tumor mass of gastric, kidney, and breast carcinoma, glioblastoma, and cardiac myxoma [13]. Interestingly, ECs of newly formed capillaries were characterized by strong MICAL2 expression; therefore, they were distinct from ECs of preformed arterioles.…”

Section: Introductionmentioning

confidence: 99%

Enriching the Arsenal of Pharmacological Tools against MICAL2

et al. 2021

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Molecule interacting with CasL 2 (MICAL2), a cytoskeleton dynamics regulator, are strongly expressed in several human cancer types, especially at the invasive front, in metastasizing cancer cells and in the neo-angiogenic vasculature. Although a plethora of data exist and stress a growing relevance of MICAL2 to human cancer, it is worth noting that only one small-molecule inhibitor, named CCG-1423 (1), is known to date. Herein, with the aim to develop novel MICAL2 inhibitors, starting from CCG-1423 (1), a small library of new compounds was synthetized and biologically evaluated on human dermal microvascular endothelial cells (HMEC-1) and on renal cell adenocarcinoma (786-O) cells. Among the novel compounds, 10 and 7 gave interesting results in terms of reduction in cell proliferation and/or motility, whereas no effects were observed in MICAL2-knocked down cells. Aside from the interesting biological activities, this work provides the first structure–activity relationships (SARs) of CCG-1423 (1), thus providing precious information for the discovery of new MICAL2 inhibitors.

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MICAL2 is expressed in cancer associated neo-angiogenic capillary endothelia and it is required for endothelial cell viability, motility and VEGF response

Cited by 16 publications

References 32 publications

Tanshinone IIA reduces secretion of pro‑angiogenic factors and inhibits angiogenesis in human colorectal cancer

Tanshinone IIA reduces secretion of pro‑angiogenic factors and inhibits angiogenesis in human colorectal cancer

Modulating Microenvironments for Treating Glioblastoma

Enriching the Arsenal of Pharmacological Tools against MICAL2

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