Lindmark G, Sundberg C, Glimelius B, Påhlman L, Rubin K, Gerdin B
Department of Surgery, University Hospital, Uppsala, Sweden.
Lab Invest. 1993 Dec;69(6):682-9.
The importance of growth factors, such as platelet-derived growth factor (PDGF), for stromal activation in colorectal cancer is unclear.
The expression of beta-receptors for PDGF, and PDGF B-chain (PDGF AB and PDGF BB) was investigated by immunohistologic techniques in full-thickness biopsies from 210 colorectal cancers. These antigens were detected by the monoclonal antibodies PDGFR-B2 and PDGF 007, respectively.
All tumors contained granular clusters of PDGF beta-receptor expressing stromal cells, whereas tumor epithelium was invariably negative. The staining was most prominent in vascular cells. There were several cells in the tumor stroma that expressed PDGF AB/BB. Double immunofluorescence stainings in specimens from four patients performed in order to characterize PDGF beta-receptor- and PDGF AB/BB expressing cells showed that cells expressing PDGF beta-receptors did not express PDGF AB/BB. About 20% of cells in the stroma expressing PDGF AB/BB were macrophages (CD68-positive cells), whereas the nature of the remaining stromal cells expressing PDGF AB/BB could not be disclosed. Furthermore, about 30% of CD68-positive macrophages expressed PDGF AB/BB, but not PDGF beta-receptors. The extent of clusters of PDGF beta-receptor expressing cells varied considerably between tumors, and its prognostic value was considered in the entire tumor material. The number of clusters did, however, not correlate to tumor differentiation, tumor stage according to Dukes', or outcome.
The presence of cells expressing PDGF beta-receptor and PDGF AB/BB respectively, i.e., expression of the receptor and its ligand, fulfills two of the prerequisites for a role of PDGF in the activation of stromal cells in colorectal cancers. The data suggest that stromal activation, characterized by clusters of PDGF beta-receptor expressing cells, is of importance for the formation of tumor stroma per se. However, the expression of the PDGF beta-receptor has no potential as a prognostic marker.
生长因子,如血小板衍生生长因子(PDGF),在结直肠癌基质激活中的重要性尚不清楚。
采用免疫组织学技术,对210例结直肠癌全层活检标本中PDGF的β受体以及PDGF B链(PDGF AB和PDGF BB)的表达情况进行研究。这些抗原分别通过单克隆抗体PDGFR - B2和PDGF 007进行检测。
所有肿瘤均含有表达PDGFβ受体的基质细胞颗粒簇,而肿瘤上皮始终为阴性。染色在血管细胞中最为明显。肿瘤基质中有多个细胞表达PDGF AB/BB。为了鉴定表达PDGFβ受体和PDGF AB/BB的细胞,对4例患者的标本进行了双重免疫荧光染色,结果显示表达PDGFβ受体的细胞不表达PDGF AB/BB。基质中约20%表达PDGF AB/BB的细胞为巨噬细胞(CD68阳性细胞),而其余表达PDGF AB/BB的基质细胞的性质尚不清楚。此外,约30%的CD68阳性巨噬细胞表达PDGF AB/BB,但不表达PDGFβ受体。表达PDGFβ受体的细胞簇的范围在肿瘤之间差异很大,并在整个肿瘤材料中考虑了其预后价值。然而,细胞簇的数量与肿瘤分化、根据Dukes分期的肿瘤阶段或预后均无相关性。
分别表达PDGFβ受体和PDGF AB/BB的细胞的存在,即受体及其配体的表达,满足了PDGF在结直肠癌基质细胞激活中发挥作用的两个先决条件。数据表明,以表达PDGFβ受体的细胞簇为特征的基质激活对于肿瘤基质本身的形成很重要。然而,PDGFβ受体的表达没有作为预后标志物的潜力。