Institute of Anatomy and Experimental Morphology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
Gut. 2013 May;62(5):741-50. doi: 10.1136/gutjnl-2011-300629. Epub 2012 Apr 5.
E- and P-selectins expressed on the luminal surface of mesodermally derived endothelial cells play a crucial role in the formation of haematogenous metastases in a number of malignancies. As peritoneal mesothelial cells are also derived form the mesoderm, it was hypothesised that selectins are also of importance in peritoneal tumour spread.
Immunohistochemistry was used to identify selectin expression on normal human peritoneum and isolated mesothelial cells. E- and P-selectin interactions with human pancreatic adenocarcinoma cells were investigated in dynamic flow assays and flow cytometry; the latter was also used to determine the main selectin ligands on pancreatic adenocarcinoma cell lines PaCa 5061, BxPC-3 and PaCa 5072, and selectin expression on human mesothelial cells. All cell lines were xenografted into the peritoneum of E- and P-selectin-deficient pfp/rag2 mice and selectin wild-type controls. Peritoneal carcinomatosis was quantified using MRI or a scoring system.
E- and P-selectin were constitutively expressed on human mesothelial and endothelial cells in the peritoneum. PaCa 5061 and BxPC-3 cells interacted with E- and P-selectins in dynamic flow assays and flow cytometry, with CA19-9 (Sialyl Lewis a) being the main E-selectin ligand. For xenografted PaCa 5061 and BxPC-3 cells, peritoneal metastasis was significantly reduced in E- and P-selectin double knockout mice compared with wild-type pfp/rag2 animals. In contrast, PaCa 5072 cells were almost devoid of selectin binding sites and no intraperitoneal tumour growth was observed.
Interactions of tumour cells with peritoneal selectins play an important role in the peritoneal spread of pancreatic adenocarcinoma.
在许多恶性肿瘤中，中胚层来源的内皮细胞管腔表面表达的 E-和 P-选择素在形成血源转移性方面起着至关重要的作用。由于腹膜间皮细胞也来源于中胚层，因此假设选择素在腹膜肿瘤扩散中也很重要。
免疫组织化学用于鉴定正常人类腹膜和分离的间皮细胞上的选择素表达。在动态流动测定和流式细胞术研究 E-和 P-选择素与人类胰腺腺癌细胞的相互作用；后者还用于确定胰腺腺癌细胞系 PaCa 5061、BxPC-3 和 PaCa 5072 上的主要选择素配体，以及人腹膜间皮细胞上的选择素表达。将所有细胞系异种移植到 E-和 P-选择素缺陷型 pfp/rag2 小鼠和选择素野生型对照的腹膜中。使用 MRI 或评分系统定量评估腹膜癌病。
E-和 P-选择素在人类腹膜中的间皮细胞和内皮细胞中持续表达。在动态流动测定和流式细胞术研究中，PaCa 5061 和 BxPC-3 细胞与 E-和 P-选择素相互作用，CA19-9（唾液酸化 Lewis a）是主要的 E-选择素配体。对于异种移植的 PaCa 5061 和 BxPC-3 细胞，与野生型 pfp/rag2 动物相比，E-和 P-选择素双敲除小鼠中的腹膜转移明显减少。相比之下，PaCa 5072 细胞几乎没有选择素结合位点，并且没有观察到腹腔内肿瘤生长。
肿瘤细胞与腹膜选择素的相互作用在胰腺腺癌的腹膜扩散中起着重要作用。
