Nelson Gregory M, Padera Timothy P, Garkavtsev Igor, Shioda Toshi, Jain Rakesh K
Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Neoplasia. 2007 Dec;9(12):1038-45. doi: 10.1593/neo.07643.
Blood vascular endothelial cells (BECs) and the developmentally related lymphatic endothelial cells (LECs) create complementary, yet distinct vascular networks. Each endothelial cell type interacts with flowing fluid and circulating cells, yet each vascular system has evolved specialized gene expression programs and thus both cell types display different phenotypes. BECs and LECs express distinct genes that are unique to their specific vascular microenvironment. Tumors also take advantage of the molecules that are expressed in these vascular systems to enhance their metastatic potential. We completed transcriptome analyses on primary cultured LECs and BECs, where each comparative set was isolated from the same individual. Differences were resolved in the expression of several major categories, such as cell adhesion molecules (CAMs), cytokines, and cytokine receptors. We have identified new molecules that are associated with BECs (e.g., claudin-9, CXCL11, neurexin-1, neurexin-2, and the neuronal growth factor regulator-1) and LECs (e.g., claudin-7, CD58, hyaluronan and proteoglycan link protein 1 (HAPLN1), and the poliovirus receptor-related 3 molecule) that may lead to novel therapeutic treatments for diseases of lymphatic or blood vessels, including metastasis of cancer to lymph nodes or distant organs.
血管内皮细胞(BECs)和发育相关的淋巴管内皮细胞(LECs)形成互补但不同的血管网络。每种内皮细胞类型都与流动的液体和循环细胞相互作用,但每个血管系统都进化出了专门的基因表达程序,因此两种细胞类型都表现出不同的表型。BECs和LECs表达其特定血管微环境特有的不同基因。肿瘤也利用这些血管系统中表达的分子来增强其转移潜能。我们对原代培养的LECs和BECs进行了转录组分析,每个比较组均从同一个体中分离得到。在细胞黏附分子(CAMs)、细胞因子和细胞因子受体等几个主要类别中,差异得以区分。我们已经鉴定出与BECs相关的新分子(例如,claudin-9、CXCL11、neurexin-1、neurexin-2和神经生长因子调节因子-1)和与LECs相关的新分子(例如,claudin-7、CD58、透明质酸和蛋白聚糖连接蛋白1(HAPLN1)以及脊髓灰质炎病毒受体相关3分子),这些分子可能会为淋巴管或血管疾病,包括癌症转移至淋巴结或远处器官带来新的治疗方法。