Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy.
Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy.
J Thromb Haemost. 2022 Mar;20(3):648-660. doi: 10.1111/jth.15611. Epub 2022 Jan 11.
Trousseau sign was the first demonstration of a close relationship between cancer and thrombosis. Currently, venous thromboembolism (VTE) is five to six times more likely to occur in cancer patients, whereas there is a greater risk of cancer diagnoses following thromboses. In considering novel players, factor VIII (FVIII), an essential coagulation cofactor with emerging extracoagulative functions, has been identified as an independent VTE risk factor in cancer; however, the basis of this increase is unknown.
To investigate the possible direct expression and secretion of FVIII by cancer cells.
Bladder cancer, with a high VTE risk, and normal bladder tissue and epithelium, were used to investigate FVIII. Factor VIII protein and secretion were examined in bladder cancer cell lines. Expanding to other cancers, the Cancer Cell line Encyclopedia database was used to analyze FVIII, tissue factor, FV, FVII, FIX, FX, and von Willebrand factor (VWF) mRNA in 811 cell lines subdivided according to origin. Factor VIII protein synthesis, secretion, and bioactivity were investigated in a profile of cancer cell lines of differing origins.
Although expressed in the normal bladder epithelium, FVIII mRNA and protein were higher in matched bladder neoplasms, with synthesis and secretion of bioactive FVIII evident in bladder cancer cells. This can be extended to other cancer cell lines, with a pattern reflecting the tumor origin, and that is independent of VWF and other relevant players in the coagulation cascade. Here, evidence is provided of a possible independent role for FVIII in cancer-related pathophysiology.
特鲁索征是癌症与血栓之间密切关系的首次证明。目前，癌症患者发生静脉血栓栓塞症（VTE）的可能性是普通人群的五到六倍，而血栓形成后发生癌症的风险更高。在考虑新的参与者时，作为一种具有新兴的非凝血功能的必需凝血辅助因子，因子 VIII（FVIII）已被确定为癌症中 VTE 的独立危险因素；然而，这种增加的基础尚不清楚。
研究癌细胞中 FVIII 可能的直接表达和分泌。
膀胱癌具有较高的 VTE 风险，使用膀胱癌和正常膀胱组织及上皮来研究 FVIII。检测了膀胱癌细胞系中的 FVIII 蛋白和分泌情况。扩展到其他癌症，使用癌症细胞系百科全书数据库来分析 811 种根据起源细分的细胞系中的 FVIII、组织因子、FV、FVII、FIX、FX 和血管性血友病因子（VWF）mRNA。在不同起源的癌症细胞系谱中研究了 FVIII 蛋白的合成、分泌和生物活性。
尽管在正常膀胱上皮中表达，但 FVIII mRNA 和蛋白在匹配的膀胱肿瘤中更高，在膀胱癌细胞中可见生物活性 FVIII 的合成和分泌。这可以扩展到其他癌细胞系，其模式反映了肿瘤起源，并且独立于 VWF 和凝血级联中的其他相关因子。这里提供了 FVIII 在癌症相关病理生理学中可能起独立作用的证据。
