The contribution of tumor-associated macrophages in glioma neo-angiogenesis and implications for anti-angiogenic strategies

Zhu, Changbin; Kros, Johan M.; Cheng, Caroline; Mustafa, Dana A. M.

doi:10.1093/neuonc/nox081

Cited by 141 publications

(130 citation statements)

References 115 publications

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“…Malignant potential of glioma cells depends critically on their capacity to transgress through the basement membrane [135,136], migrate through the extracellular matrix [137], reach and enter proximally located microvasculature, travel to distant sites [138], exit the microvasculature, and implant and grow in distant microenvironments [139]. Neoangiogenesis induced by protein factors released from glioma cells contributes to sustaining tumoral growth [140]. Evasion of immune responses by downregulation of cell surface expression of tumor specific antigens and negative immunomodulators contributes to immune evasion by glioma cells [125].…”

Section: Drug Developmentmentioning

confidence: 99%

RETRACTED ARTICLE: β adrenergic receptor modulated signaling in glioma models: promoting β adrenergic receptor-β arrestin scaffold-mediated activation of extracellular-regulated kinase 1/2 may prove to be a panacea in the treatment of intracranial and spinal malignancy and extra-neuraxial carcinoma

Ghali

2020

Mol Biol Rep

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Neoplastically transformed astrocytes express functionally active cell surface β adrenergic receptors (βARs). Treatment of glioma models in vitro and in vivo with β adrenergic agonists variably amplifies or attenuates cellular proliferation. In the majority of in vivo models, β adrenergic agonists generally reduce cellular proliferation. However, treatment with β adrenergic agonists consistently reduces tumor cell invasive potential, angiogenesis, and metastasis. β adrenergic agonists induced decreases of invasive potential are chiefly mediated through reductions in the expression of matrix metalloproteinases types 2 and 9. Treatment with β adrenergic agonists also clearly reduce tumoral neoangiogenesis, which may represent a putatively useful mechanism to adjuvantly amplify the effects of bevacizumab. Bevacizumab is a monoclonal antibody targeting the vascular endothelial growth factor receptor. We may accordingly designate βagonists to represent an enhancer of bevacizumab. The antiangiogenic effects of β adrenergic agonists may thus effectively render an otherwise borderline effective therapy to generate significant enhancement in clinical outcomes. β adrenergic agonists upregulate expression of the major histocompatibility class II DR alpha gene, effectively potentiating the immunogenicity of tumor cells to tumor surveillance mechanisms. Authors have also demonstrated crossmodal modulation of signaling events downstream from the β adrenergic cell surface receptor and microtubular polymerization and depolymerization. Complex effects and desensitization mechanisms of the β adrenergic signaling may putatively represent promising therapeutic targets. Constant stimulation of the β adrenergic receptor induces its phosphorylation by β adrenergic receptor kinase (βARK), rendering it a suitable substrate for alternate binding by β arrestins 1 or 2. The binding of a β arrestin to βARK phosphorylated βAR promotes receptor mediated internalization and downregulation of cell surface receptor and contemporaneously generates a cell surface scaffold at the βAR. The scaffold mediated activation of extracellular regulated kinase 1/2, compared with protein kinase A mediated activation, preferentially favors cytosolic retention of ERK1/2 and blunting of nuclear translocation and ensuant pro-transcriptional activity. Thus, βAR desensitization and consequent scaffold assembly effectively retains the cytosolic homeostatic functions of ERK1/2 while inhibiting its pro-proliferative effects. We suggest these mechanisms specifically will prove quite promising in developing primary and adjuvant therapies mitigating glioma growth, angiogenesis, invasive potential, and angiogenesis. We suggest generating compounds and targeted mutations of the β adrenergic receptor favoring β arrestin binding and scaffold facilitated activation of ERK1/2 may hold potential promise and therapeutic benefit in adjuvantly treating most or all cancers. We hope our discussion will generate fruitful research endeavors seeking to exploit these mechanisms.

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Section: Drug Developmentmentioning

confidence: 99%

RETRACTED ARTICLE: β adrenergic receptor modulated signaling in glioma models: promoting β adrenergic receptor-β arrestin scaffold-mediated activation of extracellular-regulated kinase 1/2 may prove to be a panacea in the treatment of intracranial and spinal malignancy and extra-neuraxial carcinoma

Ghali

2020

Mol Biol Rep

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“…A few studies have demonstrated that the amount of TAMs in a tumor are closely linked to the number of blood vessels in human cancers [43-46]. Tumor growth is characterized by hypoxia, therefore macrophages are recruited to hypoxic areas of the tumor.…”

Section: The Role Of Tams On Tumor Angiogenesis Crc Growthmentioning

confidence: 99%

The Role of Tumor-Associated Macrophages in Colorectal Carcinoma Progression

Zhong¹,

Chen²,

Yang³

2018

Cell Physiol Biochem

103

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Tumor-associated macrophages (TAMs) are one of the most abundant immune cells in the tumor microenvironment, and they play a pivotal role in prompting the various tumor growth. However, the role of TAMs in colorectal carcinoma (CRC) is controversial, because a few papers report that TAMs is beneficial to CRC patients. In this review, we discuss the good or bad roles of TAMs in CRC progression. Interestingly, recent studies provide strong evidence that TAMs facilitate CRC growth, but do not exert tumor suppressive activities. TAMs can stimulate CRC growth by altering extracellular matrix remodeling, tumor metabolism, angiogenesis, as well as the tumor microenvironment. Therefore, TAMs could serve as a target for CRC therapeutic treatment.

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“…We wanted to investigate whether AVNP2 had a similar effect on gliomas. This time, we found that AVNP2 could not only modulate the tumour associated inflammation but also the levels of inflammation-related proteins such as IL-1β, IL-6, TNF-α and NF-ĸB, which all together play an indispensable role in the formation, growth, infiltration and metastasis of gliomas (Zhu et al, 2017).…”

Section: Discussionmentioning

confidence: 90%

AVNP2 protects against cognitive impairments induced by C6 glioma by suppressing tumour associated inflammation in rats

Liu

Gao

et al. 2020

Brain, Behavior, and Immunity

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The contribution of tumor-associated macrophages in glioma neo-angiogenesis and implications for anti-angiogenic strategies

Cited by 141 publications

References 115 publications

The Role of Tumor-Associated Macrophages in Colorectal Carcinoma Progression

AVNP2 protects against cognitive impairments induced by C6 glioma by suppressing tumour associated inflammation in rats

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