Urothelial Carcinoma of the Bladder Induces Endothelial Cell Activation and Hypercoagulation

John, Axel; Robador, José R.; Vidal-y-Sy, Sabine; Houdek, Pia; Wladykowski, Ewa; Güneş, Çagatay; Bolenz, Christian; Schneider, Stefan W.; Bauer, Alexander; Gorzelanny, Christian

doi:10.1158/1541-7786.mcr-19-1041

Cited by 23 publications

(26 citation statements)

References 65 publications

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“…qRT-PCR was performed as previously reported [47]. Briefly, Total RNA was extracted using the RNeasy Plus Mini Kit (Qiagen, Hilden, Germany) according to the manufacturer's protocol and qRT-PCR was performed using the Reverse Transcription System and the GoTaq qPCR Master Mix (Promega, Heidelberg, Germany).…”

Section: Qrt-pcrmentioning

confidence: 99%

Melanoma Associated Chitinase 3-Like 1 Promoted Endothelial Cell Activation and Immune Cell Recruitment

Ramos-Espinosa

Wang

Brandner

et al. 2021

IJMS

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Chitinase 3-like 1 (CHI3L1) is an enzymatically inactive mammalian chitinase that is associated with tumor inflammation. Previous research indicated that CHI3L1 is able to interact with different extracellular matrix components, such as heparan sulfate. In the present work, we investigated whether the interaction of CHI3L1 with the extracellular matrix of melanoma cells can trigger an inflammatory activation of endothelial cells. The analysis of the melanoma cell secretome indicated that CHI3L1 increases the abundance of various cytokines, such as CC-chemokine ligand 2 (CCL2), and growth factors, such as vascular endothelial growth factor A (VEGF-A). Using a solid-phase binding assay, we found that heparan sulfate-bound VEGF-A and CCL2 were displaced by recombinant CHI3L1 in a dose-dependent manner. Microfluidic experiments indicated that the CHI3L1 altered melanoma cell secretome promoted immune cell recruitment to the vascular endothelium. In line with the elevated VEGF-A levels, CHI3L1 was also able to promote angiogenesis through the release of extracellular matrix-bound pro-angiogenic factors. In conclusion, we showed that CHI3L1 is able to affect the tumor cell secretome, which in turn can regulate immune cell recruitment and blood vessel formation. Accordingly, our data suggest that the molecular targeting of CHI3L1 in the course of cancer immunotherapies can tune patients’ response and antitumoral inflammation.

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Section: Qrt-pcrmentioning

confidence: 99%

Melanoma Associated Chitinase 3-Like 1 Promoted Endothelial Cell Activation and Immune Cell Recruitment

Ramos-Espinosa

Wang

Brandner

et al. 2021

IJMS

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“…Previously, we showed that platelets could be trapped at the vessel wall by ultralarge vWF fibres released from activated endothelial cells through a VEGF-A mediated signalling [26]. However, our previous research indicated that the SN of T24 cells was unable to instantaneously mediate the release of vWF from HUVECs [26]. Here, we measured the binding of platelets upon prolonged pre-treatment of the HUVECs (6 h) with T24 cell SN (Fig.…”

Section: Ubc Cell Induced Platelet Binding and Leukocyte Recruitmentmentioning

confidence: 80%

“…We measured platelet binding (platelet covered area) as an indicator of pro-thrombotic endothelial cell activation. Previously, we showed that platelets could be trapped at the vessel wall by ultralarge vWF fibres released from activated endothelial cells through a VEGF-A mediated signalling [26]. However, our previous research indicated that the SN of T24 cells was unable to instantaneously mediate the release of vWF from HUVECs [26].…”

Section: Ubc Cell Induced Platelet Binding and Leukocyte Recruitmentmentioning

confidence: 96%

Bladder cancer-derived interleukin-1 converts the vascular endothelium into a pro-inflammatory and pro-coagulatory surface

et al. 2020

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Background Bladder cancer cells orchestrate tumour progression by pro-inflammatory cytokines. Cytokines modulate the local tumour microenvironment and increase the susceptibility of tumour distant tissues for metastasis. Here, we investigated the impact of human bladder cancer cell derived factors on the ability to modulate and activate human vascular endothelial cells. Methods The pro-inflammatory and pro-coagulatory potential of four different bladder cancer cell lines was accessed by qRT-PCR arrays and ELISA. Modulation and activation of endothelial cells was studied in microfluidic devices. Clinical relevance of our findings was confirmed by immune histology in tissue samples of bladder cancer patients and public transcriptome data. Results The unbalanced ratio between interleukin (IL)-1 and IL-1 receptor antagonist (IL-1ra) in the secretome of bladder cancer cells converted the quiescent vascular endothelium into a pro-adhesive, pro-inflammatory, and pro-coagulatory surface. Microfluidic experiments showed that tumour cell induced endothelial cell activation promoted leukocyte recruitment and platelet adhesion. Human bladder cancer tissue analysis confirmed that loss of IL-1ra and elevated IL-1 expression was associated with enhanced cancer progression. Conclusions Our data indicate that IL-1 and IL-1ra were dysregulated in bladder cancer and could facilitate tumour dissemination through endothelial cell activation. Targeting the IL-1/IL-1ra axis might attenuate tumour-mediated inflammation and metastasis formation.

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“…Similarly, tumor cells have also been shown to secrete soluble factors that induce WPB exocytosis. For example, tumor secretomes derived from lung (A549) cells, prostate (PC3) cells, urothelial carcinoma (RT4) cells, colon cancer (HT‐29) cells, and melanoma (MV3, BLM) cells were able to promote VWF secretion from primary human ECs in vitro 32‐38 . Thus, tumor‐mediated VWF secretion from ECs is likely to contribute to the elevated plasma VWF:Ag reported in these patient cohorts.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, tumor‐mediated VWF secretion from ECs is likely to contribute to the elevated plasma VWF:Ag reported in these patient cohorts. The biological mechanisms through which the tumor secretome induces EC activation is varied, but includes inflammatory cytokines (IL‐6 and −8), matrix metalloproteinases (MMP‐1 and MMP‐2), and angiogenic mediators (vascular endothelial growth factor A [VEGF‐A]) 32‐38 …”

Section: Introductionmentioning

confidence: 99%

Von Willebrand factor and cancer; metastasis and coagulopathies

Patmore

Dhami

O’Sullivan

2020

Journal of Thrombosis and Haemostasis

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Von Willebrand factor (VWF) is a complex multimeric plasma glycoprotein critical for normal hemostatic function. VWF has two main roles in hemostasis: first, to recruit and tether platelets at sites of vascular injury, facilitating platelet aggregation. Second, VWF acts as a protective carrier molecule for procoagulant factor VIII (FVIII). 1 Under physiological conditions VWF biosynthesis is restricted to endothelial cells (EC) and megakaryocytes. Within ECs, VWF can be constitutively secreted from both the luminal and abluminal membrane or stored in specialized organelles known as Weibel-Palade bodies (WPB). In contrast, platelets store VWF in α-granules, which is released upon activation. 2 Within plasma, mature VWF circulates as a series of large heterogeneous multimers composed of repeating monomeric units, up

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Urothelial Carcinoma of the Bladder Induces Endothelial Cell Activation and Hypercoagulation

Cited by 23 publications

References 65 publications

Melanoma Associated Chitinase 3-Like 1 Promoted Endothelial Cell Activation and Immune Cell Recruitment

Melanoma Associated Chitinase 3-Like 1 Promoted Endothelial Cell Activation and Immune Cell Recruitment

Bladder cancer-derived interleukin-1 converts the vascular endothelium into a pro-inflammatory and pro-coagulatory surface

Von Willebrand factor and cancer; metastasis and coagulopathies

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