Bladder cancer-derived interleukin-1 converts the vascular endothelium into a pro-inflammatory and pro-coagulatory surfa
- PDF / 2,272,347 Bytes
- 13 Pages / 595.276 x 790.866 pts Page_size
- 77 Downloads / 144 Views
RESEARCH ARTICLE
Open Access
Bladder cancer-derived interleukin-1 converts the vascular endothelium into a pro-inflammatory and pro-coagulatory surface A. John1, C. Günes1, C. Bolenz1, S. Vidal-y-Sy2, A. T. Bauer2, S. W. Schneider2 and C. Gorzelanny2*
Abstract 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 procoagulatory 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. Keywords: Tumour microenvironment, von Willebrand factor, Coagulation, Inflammation, Endothelial cells
Background Advanced urothelial bladder cancer (UBC) is characterized by poor prognosis and a median survival of only 14 months after first line chemotherapy with gemcitabine and cisplatin [1]. High metastatic potential and limited treatment alternatives for patients not eligible for or * Correspondence: [email protected] 2 Department of Dermatology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany Full list of author information is available at the end of the article
refractory to platinum-based combination chemotherapy present major therapeutic challenges. Although immunomodulatory therapies using checkpoint inhibition, present promising options in metastatic disease, their administration can induce severe autoimmunity related side effects and response rates are in the range of only 20–30% [2]. Tumour progression is linked to local and systemic proinflammatory and pro-thrombotic intravascular conditions [3]. Consequently, risk of thromboembolism is high in cancer patients and represents the second leading cause of
© The Author(s). 2020 Open Access This article is licensed under a Creative Comm
Data Loading...
