Mikuła-Pietrasik Justyna, Uruski Paweł, Kucińska Małgorzata, Tykarski Andrzej, Książek Krzysztof
Department of Hypertensiology, Angiology and Internal Medicine, Poznań University of Medical Sciences, Długa 1/2 Str., 61-848 Poznań, Poland.
Department of Toxicology, Poznań University of Medical Sciences, Dojazd 30 Str., 60-631 Poznań, Poland.
Int J Biochem Cell Biol. 2017 May;86:26-31. doi: 10.1016/j.biocel.2017.03.013. Epub 2017 Mar 18.
In this project we examined how the presence of human peritoneal mesothelial cells (HPMCs) modifies (supports or inhibits) colorectal and pancreatic cancer cell progression in mice peritoneal cavity. Experiments were performed using primary, omentum-derived HPMCs, commercially available colorectal (SW-480) and pancreatic (PSN-1) cancer cells, and immunocompromised SCID mice. Tumor growth within the peritoneal cavity was monitored using bioluminescence. Adhesion of the cancer cells to HPMCs was examined using a fluorescence-based method, while the incidence of apoptosis was quantified using flow cytometry. Experiments showed that SW480 and PSN-1 cells formed tumors in vivo at higher efficiency when they were injected alone than in the presence of HPMCs. In vitro investigations confirmed that firm adhesion of SW480 and PSN-1 cells to HPMCs is mediated by interactions between ICAM-1 and CD43. They also revealed that IL-6 and TNFα up-regulate the expression of cell-bound ICAM-1 and the secretion of soluble ICAM-1 (sICAM-1). The basal release of sICAM-1 by HPMCs positively correlated with the expression of the cell-bound molecule. sICAM-1 inhibited dose-dependently the adhesion of SW480 and PSN-1 cells to HPMCs. Cancer cells that did not adhere to HPMCs displayed increased activity of caspase-3 and -9, increased incidence of apoptosis, and an inability to re-adhesion, as compared with their intact counterparts not exposed to sICAM-1. Our findings indicate that under certain conditions HPMCs are capable of inhibiting growth of gastrointestinal tumors in a mechanism involving the anti-adhesive capabilities of sICAM-1.
在本项目中，我们研究了人腹膜间皮细胞（HPMC）的存在如何改变（促进或抑制）小鼠腹腔内结肠和胰腺癌细胞的进展。实验使用源自大网膜的原代HPMC、市售结肠癌细胞（SW-480）和胰腺癌细胞（PSN-1）以及免疫缺陷的SCID小鼠进行。使用生物发光监测腹腔内肿瘤的生长。使用基于荧光的方法检测癌细胞与HPMC的粘附，同时使用流式细胞术对细胞凋亡发生率进行定量。实验表明，SW480和PSN-1细胞单独注射时在体内形成肿瘤的效率高于与HPMC共同存在时。体外研究证实，SW480和PSN-1细胞与HPMC的牢固粘附是由ICAM-1和CD43之间的相互作用介导的。研究还显示，IL-6和TNFα上调细胞结合型ICAM-1的表达以及可溶性ICAM-1（sICAM-1）的分泌。HPMC释放的基础sICAM-1与细胞结合型分子的表达呈正相关。sICAM-1剂量依赖性地抑制SW480和PSN-1细胞与HPMC的粘附。与未暴露于sICAM-1的完整对应细胞相比，未粘附于HPMC的癌细胞显示出caspase-3和-9活性增加、细胞凋亡发生率增加以及无法重新粘附。我们的研究结果表明，在某些条件下，HPMC能够通过涉及sICAM-1抗粘附能力的机制抑制胃肠道肿瘤的生长。
