Expression of activated platelet-derived growth factor receptor in stromal cells of human colon carcinomas is associated with metastatic potential
Expression of activated platelet-derived growth factor receptor in stromal cells of human colon carcinomas is associated with metastatic potential
复制标题
DOI：
10.1002/ijc.22229
复制
发表时间：
2006-12-01
影响因子：
6.4
通讯作者：
Fidler, Isaiah J.
中科院分区：
文献类型：
--
作者：
Kitadai, Yasuhiko;Sasaki, Takamitsu;Fidler, Isaiah J.
血小板衍生生长因子受体（PDGF-R）表达已被报道在各种癌症，包括结肠直肠癌，乳腺癌，肺癌，卵巢癌和胰腺癌，但PDGF-R表达在结肠癌的发展和进展中的作用尚未阐明。本研究的目的是检测血小板衍生生长因子（PDGF）和血小板衍生生长因子受体（PDGF-R）在人结肠癌中的表达。用免疫荧光法检测了12例结肠癌手术标本及裸鼠皮下（异位部位）和盲肠壁（原位部位）人结肠癌细胞中PDGF、PDGF-R和磷酸化PDGF-R（p-PDGF-R）的表达。在大多数手术标本中，肿瘤细胞表达PDGF-A和-B亚基，而没有相应水平的PDGF-R α和PDGF-R β。PDGF-R β主要由肿瘤相关基质细胞和肿瘤血管周细胞表达。间质中PDGF-R β的表达与晚期疾病相关。在培养条件下，人结肠癌细胞系表达PDGF-A和-B，但不表达PDGF-R。在原位肿瘤中，KM 12细胞（杜克氏分期B）表达PDGF-A和-B，但PDGF-R β仅由肿瘤血管系统中的基质细胞和周细胞表达。在原位生长的肿瘤中，基质细胞和周细胞的PDGF-R β表达高于异位生长的肿瘤。高转移性KM 12 SM肿瘤间质中PDGF-R β的表达高于低转移性KM 12 C肿瘤。总之，PDGF-R β在基质细胞中的表达受到器官特异性微环境的影响，并与转移潜能相关。(c)2006 Wiley-Liss，Inc.
Platelet-derived growth factor receptor (PDGF-R) expression has been reported in a variety of cancers, including colorectal, breast, lung, ovarian and pancreatic cancers, but the role of PDGF-R expression in the development and progression of colon carcinoma has not yet been elucidated. The purpose of this study was to examine the expression of PDGF and PDGF-R in human colon carcinomas. The expression of PDGF, PDGF-R and phosphorylated PDGF-R (p-PDGF-R) was examined by immunofluorescence in 12 surgical specimens of colon carcinoma and in human colon carcinoma cells growing in the subcutis (ectopic site) and the cecal wall (orthotopic site) of nude mice. In most surgical specimens, tumor cells expressed PDGF-A and -B subunits, without corresponding levels of PDGF-R alpha and PDGF-R beta. PDGF-R beta was predominantly expressed by tumor-associated stromal cells and pericytes of tumor vasculature. The expression of PDGF-R beta in the stroma was associated with advanced stage disease. Under culture conditions, human colon carcinoma cell lines expressed PDGF-A and -B, but not PDGF-R. In orthotopic tumors, the KM12 cells (Duke's stage B) expressed PDGF-A and -B, but PDGF-R beta was expressed only by stromal cells and pericytes in the tumor vasculature. This expression of PDGF-R beta by stromal cells and pericytes was higher in tumors growing at the orthotopic site than in those at the ectopic site. The expression of PDGF-R beta in the stroma was higher in highly metastatic KM12SM tumors than in low metastatic KM12C tumors. In conclusion, the expression of PDGF-R beta in stromal cells is influenced by the organ-specific microenvironment and is associated with metastatic potential. (c) 2006 Wiley-Liss, Inc.