Cellular changes in the tumor microenvironment of human esophageal squamous cell carcinomas

Cellular changes in the tumor microenvironment of human esophageal squamous cell carcinomas
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DOI:
10.1007/s13277-011-0281-3
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发表时间:
2012-04-01
期刊:
影响因子:
--
通讯作者:
Cui, Guanglin
Cui, Guanglin
中科院分区:
其他
文献类型:
--
作者:
Liu, Jinzhong;Li, Zhenfeng;Cui, Guanglin

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人类癌症的生长、侵袭和转移不仅取决于癌细胞,而且还取决于它们的微环境。本研究的目的是扩展我们以前的研究,并检测食管鳞癌(ESCCs)肿瘤微环境(间质)中细胞的变化。用免疫组织化学方法检测不同间质(非肿瘤间质、肿瘤间质和肿瘤周围间质)的增殖活性、细胞成分和血管生成情况。结果显示,与非肿瘤区基质细胞相比,肿瘤组织中Ki-67标记的间质细胞具有高增殖率,导致肿瘤间质中肌成纤维细胞(SMA-α标记)、淋巴细胞(CD3标记)、巨噬细胞(CD68标记)密度增加,以微血管密度(MVD)增加和血管生成因子(血管内皮生长因子和白介素8)表达增加为特征的血管生成激活。进一步分析发现,瘤周间质区的间质细胞密度变化较瘤巢间质区明显。大多数细胞改变与淋巴转移显著相关。免疫组织化学双重染色结果显示,食管癌间质中的这些细胞具有一定的增殖能力。存在于肿瘤微环境中的细胞被激活,提示微环境成分可能参与了肿瘤的生长和发展。
The growth, invasiveness, and metastasis of human cancers are not only determined by the cancer cells but also by their microenvironment. The purpose of this study was to extend our previous studies and to examine the cellular changes in tumor microenvironment (stroma) of esophageal squamous cell carcinomas (ESCCs). The proliferative activity, cellular components, and angiogenesis status in different compartments (non-tumor stroma, tumor stroma, and tumor periphery stroma) of ESCCs were evaluated by immunohistochemistry. The results revealed a hyperproliferative rate labeled by Ki-67 in stromal cells in tumor area as compared with that in stromal cells in non-tumor area, which resulted in the increased densities of myofibroblasts (labeled by smooth muscle actin (SMA)-alpha), lymphocytes (labeled by CD3), macrophages (labeled by CD68), and the activation of angiogenesis characterized by increased microvessel density (MVD) and the increased expression of the proangiogenic factors (vascular endothelial growth factor and interleukin 8) in the tumor stroma. Further analysis showed that the changes of stromal cell density were more significant in the area of periphery tumor stroma than that of stroma between tumor nests. Most cellular changes were significantly associated with lymph node involvement. Double immunohistochemistries with PCNA/CD3, PCNA/CD68, and PCNA/SMA-alpha revealed that these cells present in the ESCC tumor stroma had a proliferative capacity. The cells present in the tumor microenvironment of ESCCs were greatly activated, suggesting that microenvironmental components may be involved in the cancer growth and progression.