Role of angiogenesis in urothelial bladder carcinoma

Fus, Łukasz; Górnicka, Barbara

doi:10.5173/ceju.2016.830

Cited by 27 publications

(15 citation statements)

References 33 publications

(45 reference statements)

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“…Angiogenesis is one of the most important factors in BCa progression 16 . BCa cells in tumor tissue may affect the vascular endothelium and therefore the interaction between BCa cells and microvascular endothelial cells via angiogenesis-related cytokines that play a crucial role in disease progression.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of angiogenesis by leflunomide via targeting the soluble ephrin-A1/EphA2 system in bladder cancer

Chu

Zhang

2018

Sci Rep

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Angiogenesis plays an important role in bladder cancer (BCa). The immunosuppressive drug leflunomide has attracted worldwide attention. However, the effects of leflunomide on angiogenesis in cancer remain unclear. Here, we report the increased expression of soluble ephrin-A1 (sEphrin-A1) in supernatants of BCa cell lines (RT4, T24, and TCCSUP) co-cultured with human umbilical vein endothelial cells (HUVECs) compared with that in immortalized uroepithelial cells (SV-HUC-1) co-cultured with HUVECs. sEphrin-A1 is released from BCa cells as a monomeric protein that is a functional form of the ligand. The co-culture supernatants containing sEphrin-A1 caused the internalization and down-regulation of EphA2 on endothelial cells and dramatic functional activation of HUVECs. This sEphrin-A1/EphA2 system is mainly functional in regulating angiogenesis in BCa tissue. We showed that leflunomide (LEF) inhibited angiogenesis in a N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced bladder carcinogenesis model and a tumor xenograft model, as well as in BCa cell and HUVEC co-culture systems, via significant inhibition of the sEphrin-A1/EphA2 system. Ephrin-A1 overexpression could partially reverse LEF-induced suppression of angiogenesis and subsequent tumor growth inhibition. Thus, LEF has a significant anti-angiogenesis effect on BCa cells and BCa tissue via its inhibition of the functional angiogenic sEphrin-A1/EphA2 system and may have potential for treating BCa beyond immunosuppressive therapy.

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Section: Discussionmentioning

confidence: 99%

Inhibition of angiogenesis by leflunomide via targeting the soluble ephrin-A1/EphA2 system in bladder cancer

Chu

Zhang

2018

Sci Rep

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“…The formation of neovasculature through angiogenic processes is vital for cancer cell proliferation and tumor progression to metastasis (168). Historically, tumor angiogenesis was perceived as being primarily regulated by cancer cells expressing proangiogenic factors; however, now it becomes increasingly clear that the tumor microenvironment is a key factor inducing and sustaining chronic angiogenesis, including in a glycosylation-dependent manner.…”

Section: Tumor Microenvironment and Glycosylation Crosstalk Toward Thmentioning

confidence: 99%

Protein Glycosylation and Tumor Microenvironment Alterations Driving Cancer Hallmarks

et al. 2019

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Decades of research have disclosed a plethora of alterations in protein glycosylation that decisively impact in all stages of disease and ultimately contribute to more aggressive cell phenotypes. The biosynthesis of cancer-associated glycans and its reflection in the glycoproteome is driven by microenvironmental cues and these events act synergistically toward disease evolution. Such intricate crosstalk provides the molecular foundations for the activation of relevant oncogenic pathways and leads to functional alterations driving invasion and disease dissemination. However, it also provides an important source of relevant glyco(neo)epitopes holding tremendous potential for clinical intervention. Therefore, we highlight the transversal nature of glycans throughout the currently accepted cancer hallmarks, with emphasis on the crosstalk between glycans and the tumor microenvironment stromal components. Focus is also set on the pressing need to include glycans and glycoconjugates in comprehensive panomics models envisaging molecular-based precision medicine capable of improving patient care. We foresee that this may provide the necessary rationale for more comprehensive studies and molecular-based intervention.

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“…Research of bladder cancer has demonstrated that angiogenesis has an important role in bladder cancer progression (19). It was demonstrated that CD31 had a strong positive expression in bladder cancer, and a weak negative expression in normal bladder tissue (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…It has previously been demonstrated that the number of ECs are increased according to tumor progression and are negatively associated with the prognosis of bladder cancer (19). In the present study it was hypothesized that ECs serve other direct or indirect roles in bladder cancer apart from the known metabolism-associated roles (such as oxygen supply).…”

Section: Resultsmentioning

confidence: 99%

Bladder cancer cells interact with vascular endothelial cells triggering EGFR signals to promote tumor progression

et al. 2019

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Although important progress has been made in elucidating the role of the tumor microenvironment in the development of bladder cancer, little is currently known regarding the interactions with vascular endothelial cells (ECs) that promote cancer progression. In the present study, it is reported that epidermal growth factor receptor ligands induced by the upregulation of vascular endothelial growth factor (VEGF)-A and VEGF-C via the VEGF receptor (R)2/nuclear factor-κB signaling pathway in ECs, may trigger EGFR signaling in bladder cancer cells and promote bladder cancer progression. Furthermore, the interaction between bladder cancer cells and ECs enhanced EC recruitment though the CXCL1/CXCL5/CXCL8-CXCR2 pathway. Western blotting was used to evaluate the presence of VEGFR, EGFR and nuclear factor-κB, and reverse transcription-quantitative polymerase chain reaction was used to evaluate the expression of VEGFR ligands and EGFR ligands. The present results indicate the mechanism by which the indirect interplay between bladder cancer cells and vascular ECs promotes cancer progression, through the VEGFR2 signaling pathway in vascular ECs and through the EGFR signaling pathway in bladder cancer cells.

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Role of angiogenesis in urothelial bladder carcinoma

Cited by 27 publications

References 33 publications

Inhibition of angiogenesis by leflunomide via targeting the soluble ephrin-A1/EphA2 system in bladder cancer

Inhibition of angiogenesis by leflunomide via targeting the soluble ephrin-A1/EphA2 system in bladder cancer

Protein Glycosylation and Tumor Microenvironment Alterations Driving Cancer Hallmarks

Bladder cancer cells interact with vascular endothelial cells triggering EGFR signals to promote tumor progression

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