Wang Ruoxiang, Nissen Nicholas N, Zhang Yi, Shao Chen, Chu Chia-Yi, Huynh Carissa, Posadas Edwin M, Tomlinson James S, Lewis Michael S, Pandol Stephen J
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
Front Physiol. 2022 Feb 14;13:827531. doi: 10.3389/fphys.2022.827531. eCollection 2022.
Human cancers are often complicated with increased incidences of blood vessel occlusion, which are mostly insensitive to anticoagulation therapy. We searched for causal factors of cancer-associated embolism. A total of 2,017 blood samples was examined for visible abnormalities. Examined were peripheral blood samples from cancer patients who were about to undergo surgical treatment for genitourinary, breast, gastrointestinal or abdominal tumors. Samples from ambulatory patients being treated for recurrent or castration-resistant prostate cancers were included in the study. The lipid-rich nature was studied with lipophilic stains and lipid panel analysis, while surface membrane was assessed with specific staining and antibody detection. We identified a new entity, lipid droplet-like objects or circulating fatty objects (CFOs), visible in the blood samples of many cancer patients, with the potential of causing embolism. CFOs were defined as lipid-rich objects with a membrane, capable of gaining in volume through interaction with peripheral blood mononuclear cells in culture. Blood samples from pancreatic cancer patients were found to have the highest CFO incidence and largest CFO numbers. Most noticeably, CFOs from many pancreatic cancer samples presented as large clusters entangled in insoluble fiber networks, suggestive of intravascular clotting. This study identifies CFO as an abnormal entity in cancer patient blood, and a contributory factor to intravascular embolism during cancer development and progression.
人类癌症常伴有血管闭塞发生率增加,且大多对抗凝治疗不敏感。我们寻找癌症相关栓塞的病因。共检查了2017份血液样本有无明显异常。检查对象为即将接受泌尿生殖系统、乳腺、胃肠道或腹部肿瘤手术治疗的癌症患者的外周血样本。研究纳入了正在接受复发性或去势抵抗性前列腺癌治疗的门诊患者的样本。通过亲脂性染色和血脂分析研究其富含脂质的特性,同时用特异性染色和抗体检测评估表面膜。我们发现了一种新实体,即脂质滴样物体或循环脂肪物体(CFOs),在许多癌症患者的血液样本中可见,具有导致栓塞的潜力。CFOs被定义为富含脂质且有膜的物体,能够通过与培养中的外周血单核细胞相互作用而增大体积。发现胰腺癌患者的血液样本中CFO发生率最高且数量最多。最值得注意的是,许多胰腺癌样本中的CFO呈现为大簇状,缠绕在不溶性纤维网络中,提示血管内凝血。本研究将CFO确定为癌症患者血液中的一种异常实体,以及癌症发生和发展过程中血管内栓塞的一个促成因素。