Pancreatic Research Group, South Western Sydney Clinical School, School of Medical Sciences, Faculty of Medicine, Room 505, Level 5, Wallace Wurth Building, The University of New South Wales, Sydney, NSW 2052, Australia.
Am J Pathol. 2010 Nov;177(5):2585-96. doi: 10.2353/ajpath.2010.090899. Epub 2010 Oct 7.
Pancreatic stellate cells (PSCs) produce the stromal reaction in pancreatic cancer (PC), and their interaction with cancer cells facilitates cancer progression. This study investigated the role of human PSCs (hPSCs) in the metastatic process and tumor angiogenesis using both in vivo (orthotopic model) and in vitro (cultured PSC and PC cells) approaches. A sex mismatch study (injection of male hPSCs plus female PC cells into the pancreas of female mice) was conducted to determine whether hPSCs accompany cancer cells to metastatic sites. Metastatic nodules were examined by fluorescent in situ hybridization for the presence of the Y chromosome. Angiogenesis was assessed by i) immunostaining tumors for CD31, an endothelial cell marker; and ii) quantifying human microvascular endothelial cell (HMEC-1) tube formation in vitro on exposure to conditioned media from hPSCs. Transendothelial migration was assessed in vitro by examining the movement of fluorescently labeled hPSCs through an endothelial cell monolayer. Human PSCs i) were found in multiple metastatic sites in each mouse injected with male hPSCs plus female PC cells; ii) increased CD31 expression in primary tumors from mice injected with MiaPaCa-2 and hPSCs and stimulated tube formation by HMEC-1 in vitro; and iii) exhibited transendothelial migration that was stimulated by cancer cells. Human PSCs accompany cancer cells to metastatic sites, stimulate angiogenesis, and are able to intravasate/extravasate to and from blood vessels.
胰腺星状细胞（PSCs）在胰腺癌（PC）中产生基质反应，它们与癌细胞的相互作用促进了癌症的进展。本研究采用体内（原位模型）和体外（培养的 PSC 和 PC 细胞）方法，研究了人胰腺星状细胞（hPSCs）在转移过程和肿瘤血管生成中的作用。进行了性别错配研究（将雄性 hPSCs 注射到雌性小鼠的胰腺中，再加上雌性 PC 细胞），以确定 hPSCs 是否伴随癌细胞转移到转移部位。通过荧光原位杂交检测 Y 染色体的存在来检查转移性结节。通过免疫染色检测肿瘤中 CD31（内皮细胞标志物）的表达和 ii）定量分析 hPSCs 条件培养基对人微血管内皮细胞（HMEC-1）体外管形成的影响来评估血管生成。通过检查荧光标记的 hPSCs 通过内皮细胞单层的迁移来评估体外跨内皮迁移。人 PSCs：i）在每个注射雄性 hPSCs 加雌性 PC 细胞的小鼠的多个转移部位中发现；ii）增加了注射 MiaPaCa-2 和 hPSCs 的小鼠原发性肿瘤中 CD31 的表达，并刺激了 HMEC-1 的体外管形成；iii）表现出由癌细胞刺激的跨内皮迁移。人 PSCs 伴随癌细胞转移到转移部位，刺激血管生成，并能够从血管内向血管外迁移/迁移。
