Microenvironmental regulation of tumour angiogenesis

Palma, Michele De; Biziato, Daniela; Petrova, Tatiana V.

doi:10.1038/nrc.2017.51

Cited by 1,448 publications

(1,209 citation statements)

References 224 publications

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“…Physiological angiogenesis is a sequence of cellular events comprising vascular initiation, formation, maturation, remodeling and regression, which are regulated to supply tissue requirements (5)(6)(7). It has been demonstrated that angiogenesis is essential for the growth, metastasis and development of cancer (8).…”

Section: Introductionmentioning

confidence: 99%

TSLP promotes angiogenesis of human umbilical vein endothelial cells by strengthening the crosstalk between cervical cancer cells and eosinophils

et al. 2017

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Abstract. Our previous study demonstrated that thymic stromal lymphopoietin (TSLP) secreted by cervical cancer cells promotes angiogenesis and recruitment, and regulates the function of eosinophils (EOS). However, the function of TSLP in the crosstalk between EOS and vascular endothelial cells in cancer lesions remains unknown. The aim of the present study was to investigate the effect of EOS caused by TSLP in in vitro angiogenesis of human umbilical vein endothelial cells (HUVECs). The results of the present study revealed that recombinant human TSLP protein (rhTSLP) increased the secretion of vascular endothelial growth factor (VEGF), but not fibroblast growth factors, in HL-60-eosinophils (HL-60E). Compared with cervical cancer cells (HeLa or CasKi cells) or HL-60E alone, there were increased levels of interleukin (IL)-8 and VEGF in the co-culture system between cervical cancer cells, and HL-60E cells. This effect was strengthened by rhTSLP, but inhibited by inhibiting the TSLP signal with anti-human TSLP or TSLP receptor neutralizing antibodies. The results of the tube formation assays revealed that treatment with the supernatant from cervical cancer cells and/or HL-60E resulted in an increase in angiogenesis in HUVECs, which could be decreased by TSLP or TSLPR inhibitors. The results of the present study suggested that TSLP derived of cervical cancer cells may indirectly stimulate angiogenesis of HUVECs, by upregulating IL-8 and VEGF production, in a co-culture model between cervical cancer cells and EOS, therefore promoting the development of cervical cancer.

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Section: Introductionmentioning

confidence: 99%

TSLP promotes angiogenesis of human umbilical vein endothelial cells by strengthening the crosstalk between cervical cancer cells and eosinophils

et al. 2017

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“…Angiogenesis is considered a key requirement for cancer growth and progression (109). This is highlighted by the fact that several angiogenesis inhibitors are in clinical trials for cancer treatment (110).…”

Section: Cell-non-autonomous Roles Of Hs Signaling In Cancermentioning

confidence: 99%

Heparan Sulfate and Heparan Sulfate Proteoglycans in Cancer Initiation and Progression

2018

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Heparan sulfate (HS) are complex unbranched carbohydrate chains that are heavily modified by sulfate and exist either conjugated to proteins or as free, unconjugated chains. Proteins with covalently bound Heparan sulfate chains are termed Heparan Sulfate Proteoglycans (HSPGs). Both HS and HSPGs bind to various growth factors and act as co-receptors for different cell surface receptors. They also modulate the dynamics and kinetics of various ligand-receptor interactions, which in turn can influence the duration and potency of the signaling. HS and HSPGs have also been shown to exert a structural role as a component of the extracellular matrix, thereby altering processes such as cell adhesion, immune cell infiltration and angiogenesis. Previous studies have shown that HS are deregulated in a variety of solid tumors and hematological malignancies and regulate key aspects of cancer initiation and progression. HS deregulation in cancer can occur as a result of changes in the level of HSPGs or due to changes in the levels of HS biosynthesis and remodeling enzymes. Here, we describe the major cell-autonomous (proliferation, apoptosis/senescence and differentiation) and cell-non-autonomous (angiogenesis, immune evasion, and matrix remodeling) roles of HS and HSPGs in cancer. Finally, we discuss therapeutic opportunities for targeting deregulated HS biosynthesis and HSPGs as a strategy for cancer treatment.

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“…ECM is characterized by biochemical properties specific for each tissue, and may be involved in overcoming the host’s immune surveillance [18,27,28,29]. …”

Section: Tumor Microenvironmentmentioning

confidence: 99%

“…The modulation in the number and/or function of the specific TME cells involved in tumor progression is often associated with a better outcome in cancer therapy, and for this reason, the selective inhibition of the PI3K/mTOR axis correlates not only with the efficacy in leukemias, but also improves the immunotherapy in different solid cancer [27,55]. Recent studies showed that the inhibition of different hub of PI3K/mTOR pathways impacts the different TME components (Table 2).…”

Section: Immunoregulatory Functions Of Mtormentioning

confidence: 99%

Role of mTOR Signaling in Tumor Microenvironment: An Overview

Cognetti

Bazzichetto

Falcone

et al. 2018

IJMS

114

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The mammalian target of rapamycin (mTOR) pathway regulates major processes by integrating a variety of exogenous cues, including diverse environmental inputs in the tumor microenvironment (TME). In recent years, it has been well recognized that cancer cells co-exist and co-evolve with their TME, which is often involved in drug resistance. The mTOR pathway modulates the interactions between the stroma and the tumor, thereby affecting both the tumor immunity and angiogenesis. The activation of mTOR signaling is associated with these pro-oncogenic cellular processes, making mTOR a promising target for new combination therapies. This review highlights the role of mTOR signaling in the characterization and the activity of the TME’s elements and their implications in cancer immunotherapy.

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Microenvironmental regulation of tumour angiogenesis

Cited by 1,448 publications

References 224 publications

TSLP promotes angiogenesis of human umbilical vein endothelial cells by strengthening the crosstalk between cervical cancer cells and eosinophils

TSLP promotes angiogenesis of human umbilical vein endothelial cells by strengthening the crosstalk between cervical cancer cells and eosinophils

Heparan Sulfate and Heparan Sulfate Proteoglycans in Cancer Initiation and Progression

Role of mTOR Signaling in Tumor Microenvironment: An Overview

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