TGFβ1 and HGF protein secretion by esophageal squamous epithelial cells and stromal fibroblasts in oesophageal carcinogenesis.
TGFβ1 and HGF protein secretion by esophageal squamous epithelial cells and stromal fibroblasts in oesophageal carcinogenesis.
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DOI：
10.3892/ol.2013.1409
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发表时间：
2013-08
期刊：
影响因子：
2.9
通讯作者：
Dong Z
中科院分区：
文献类型：
--
作者：
Xu Z;Wang S;Wu M;Zeng W;Wang X;Dong Z
食道鳞状细胞癌(ESCC)是一种侵袭性肿瘤，预后较差。肿瘤相关成纤维细胞通过分泌肝细胞生长因子和转化生长因子β1等因子，为肿瘤的生长和侵袭创造良好的环境，从而影响肿瘤的发生。本研究采用免疫组织化学方法检测了食管癌前病变(低度和高度上皮内瘤变)、原位癌和鳞癌组织中α-平滑肌肌动蛋白(α-SMA)、转化生长因子β-1和肝细胞生长因子的表达。在食道上皮细胞和间质成纤维细胞胞浆内可见免疫反应阳性。α-SMA、转化生长因子β-1和肝细胞生长因子的表达水平依次升高，依次为正常、低分化、鳞癌。此外，α-SMA、转化生长因子β-1和肝细胞生长因子的表达与不同的病变呈线性相关。所有标本均测得微血管密度(MVD)，正常、LGIEN、HGIEN、CIS、SCC组织中MVD依次递增。微血管密度与病理分级呈线性相关，α-β-1阳性组的微血管密度高于阴性组。结果表明，食道上皮和间质成纤维细胞分泌的转化生长因子β-1和肝细胞生长因子蛋白的频繁过表达，通过上调血管内皮生长因子的表达，促进了上皮细胞的增殖和血管生成，从而促进了食管癌前病变的进展。
Esophageal squamous cell carcinoma (ESCC) is an aggressive cancer with a poor prognosis. Cancer-associated fibroblasts (CAFs) affect tumorigenesis by creating an environment primed for growth and invasion through the secretion of factors, including hepatocyte growth factor (HGF) and transforming growth factor β1 (TGFβ1). In the present study, the levels of α-smooth muscle actin (α-SMA), TGFβ1 and HGF were determined immunohistochemically in oesophageal precancerous lesions (low- and high-grade intraepithelial neoplasia; LGIEN and HGIEN, respectively), carcinoma in situ (CIS) and squamous cell carcinoma (SCC). Immunoreactivity was observed in the cytoplasm of oesophageal epithelial cells and stromal fibroblasts. Expression levels of α-SMA, TGFβ1 and HGF increased significantly in the following order: normal, LGIEN, HGIEN, CIS and SCC. In addition, linear correlations between the expression of α-SMA, TGFβ1 and HGF and different lesions were observed. Microvessel density (MVD) was measured in all specimens and increased gradually in the normal, LGIEN, HGIEN, CIS and SCC specimens, successively. A linear correlation between MVD and pathological grade was also observed and the MVD in α-SMA-, HGF- and TGFβ1-positive groups was higher when compared with that of their negative counterparts. The results of the present study indicated that the frequent overexpression of TGFβ1 and HGF proteins, secreted by oesophageal epithelium and stromal fibroblasts, promoted the progression of oesophageal precancerous lesions via the proliferation of epithelial cells and angiogenesis, through the upregulation of vascular endothelial growth factor (VEGF) expression.
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DOI：
10.1073/pnas.0401064101
发表时间：
2004-04-06
影响因子：
11.1
作者：
Kuperwasser, C;Chavarria, T;Weinberg, RA
通讯作者：
Weinberg, RA
影响因子：
29.4
作者：
Noma, Kazuhiro;Smalley, Keiran S. M.;Herlyn, Meenhard
通讯作者：
Herlyn, Meenhard
DOI：
10.1590/s0036-36342011000500008
发表时间：
2011-10-01
期刊：
Salud Pública de México
影响因子：
--
作者：
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通讯作者：
Civetta, Julio Domingo
影响因子：
2.5
作者：
Langenskiod, Marcus;Holmdahl, Lena;Ivarsson, Marie-Louise
通讯作者：
Ivarsson, Marie-Louise
影响因子：
50.3
作者：
Erez, Neta;Truitt, Morgan;Hanahan, Douglas
通讯作者：
Hanahan, Douglas