Marlicz Wojciech, Sielatycka Katarzyna, Serwin Karol, Kubis Ewa, Tkacz Marta, Głuszko Rafał, Białek Andrzej, Starzyńska Teresa, Ratajczak Mariusz Z
Department of Gastroenterology, Pomeranian Medical University, 71-252 Szczecin, Poland.
Department of Physiology, Pomeranian Medical University, 71-252 Szczecin, Poland.
Oncol Rep. 2016 Dec;36(6):3635-3642. doi: 10.3892/or.2016.5179. Epub 2016 Oct 18.
Bone marrow (BM) residing stem cells are mobilized from their BM niches into peripheral blood (PB) in several pathological situations including tissue organ injury and systemic inflammation. We recently reported that the number of BM-derived stem cells (SCs) increases in patients with pancreatic and stomach cancer. Accordingly, we observed higher numbers of circulating very small embryonic/epiblast‑like stem cells (VSELs) and mesenchymal stem cells (MSCs) that were associated with the activation of pro-mobilizing complement cascade and an elevated level of sphingosine-1 phosphate (S1P) in PB plasma. We wondered if a similar correlation occurs in patients with colorectal cancer (CRC). A total of 46 patients were enrolled in this study: 17 with CRC, 18 with benign colonic adenomas (BCA) and 11 healthy individuals. By employing fluorescence-activated cell sorting (FACS) we evaluated the number of BM-derived SCs circulating in PB: i) CD34+/Lin-/CD45- and CD133-/Lin-/CD45- VSELs; ii) CD45-/CD105+/CD90+/CD29+ MSCs; iii) CD45-/CD34+/CD133+/KDR+ endothelial progenitor cells (EPCs); and iv) CD133+/Lin-/CD45+ or CD34+/Lin-/CD45+ cells enriched for hematopoietic stem/progenitor cells (HSPCs). In parallel, we measured in the PB parameters regulating the egress of SCs from BM into PB. In contrast to pancreatic and gastric cancer patients, CRC subjects presented neither an increase in the number of circulating SCs nor the activation of pro-mobilizing factors such as complement, coagulation and fibrinolytic cascade, circulating stromal derived factor 1 (SDF‑1), vascular endothelial growth factor (VEGF) and intestinal permeability marker (zonulin). In conclusion, mobilization of SCs in cancer patients depends on the type of malignancy and its ability to activate pro-mobilization cascades.
在包括组织器官损伤和全身性炎症在内的多种病理情况下，驻留在骨髓（BM）中的干细胞会从其骨髓微环境中动员到外周血（PB）中。我们最近报告称，胰腺癌和胃癌患者骨髓来源的干细胞（SCs）数量会增加。相应地，我们观察到循环中的极小型胚胎/类上胚层干细胞（VSELs）和间充质干细胞（MSCs）数量增多，这与促动员补体级联反应的激活以及外周血血浆中鞘氨醇-1-磷酸（S1P）水平升高有关。我们想知道在结直肠癌（CRC）患者中是否也存在类似的相关性。本研究共纳入46例患者：17例结直肠癌患者、18例良性结肠腺瘤（BCA）患者和11名健康个体。通过采用荧光激活细胞分选（FACS）技术，我们评估了外周血中循环的骨髓来源干细胞的数量：i）CD34+/Lin-/CD45-和CD133-/Lin-/CD45- VSELs；ii）CD45-/CD105+/CD90+/CD29+ MSCs；iii）CD45-/CD34+/CD133+/KDR+内皮祖细胞（EPCs）；iv）富含造血干/祖细胞（HSPCs）的CD133+/Lin-/CD45+或CD34+/Lin-/CD45+细胞。同时，我们测量了外周血中调节干细胞从骨髓进入外周血的参数。与胰腺癌和胃癌患者不同，结直肠癌患者循环干细胞数量既没有增加，也没有激活诸如补体、凝血和纤溶级联反应、循环基质衍生因子1（SDF-1）、血管内皮生长因子（VEGF）和肠道通透性标志物（闭合蛋白）等促动员因子。总之，癌症患者中干细胞的动员取决于恶性肿瘤的类型及其激活促动员级联反应的能力。
