Co-evolution of tumor-associated macrophages and tumor neo-vessels during cervical cancer invasion.
Co-evolution of tumor-associated macrophages and tumor neo-vessels during cervical cancer invasion.
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DOI：
10.3892/ol.2016.5014
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发表时间：
2016-10
期刊：
影响因子：
2.9
通讯作者：
Yuan J
中科院分区：
文献类型：
--
作者：
Jiang S;Yang Y;Fang M;Li X;Yuan X;Yuan J
鉴于肿瘤微环境在肿瘤发生发展中的重要意义，本研究旨在探讨宫颈癌从慢性宫颈炎症到宫颈上皮内瘤变I~III级(CIN I~III)再到CC过程中巨噬细胞和血管生成的变化。这项研究包括定量分析和评估肿瘤相关巨噬细胞(TAMs)和肿瘤新生血管之间的空间联系。采用免疫组织化学方法分别检测TAMs和肿瘤新生血管中分化簇(CD)68和CD105的表达。此外，借助基于量子点(QD)的双组分原位成像技术，可以同时观察TAMS和肿瘤新生血管的表达。然后对TAMs和肿瘤新生血管进行定量分析和协同进化。从慢性宫颈炎症到宫颈CIN I-III，再到侵袭性宫颈癌变的过程中，肿瘤微环境中巨噬细胞和新生血管的表达同步增加。定量分析结果显示，CC组密度中位数(5,540.14)高于CIN I-III组(2,502.17)和慢性宫颈炎组(1,403.31)，组间比较有统计学意义(P<；0.001)。CC组(n=27)新生血管数明显高于CIN I-III组(n=17)或慢性宫颈炎组(n=6.5)，三组间差异均有统计学意义(P<；0.001，组间比较)。这些结果表明TAMS与肿瘤血管生成在CC的发生发展过程中具有重要意义和密切联系。因此，基于量子点的关键癌症分子的原位和同步成像可能提供关于癌症侵袭生物学的见解。
Considering the crucial significance of the tumor microenvironment in cancer development and progression, the present study aimed to investigate the changes in macrophages and angiogenesis during the cervical cancer (CC) progression process from chronic cervicitis to cervical intraepithelial neoplasia grades I–III (CIN I–III) to CC. This investigation included quantitative analysis and assessment of the spatial associations between tumor-associated macrophages (TAMs) and tumor neo-vessels. The conventional immunohistochemistry staining technique was used to detect cluster of differentiation (CD)68 and CD105 biomarker expression for TAMs and tumor neo-vessels, respectively. In addition, with the assistance of quantum dot (QD)-based two-component in situ imaging technology, the expression of the TAMs and tumor neo-vessels could be observed simultaneously. The quantitative analysis and co-evolution of the TAMs and tumor neo-vessels could then be processed. During the progression process from chronic cervicitis to cervical CIN I–III, and ultimately to invasive CC, the expression of the macrophages and neo-vessels in the tumor microenvironment increased synchronously. According to the quantitative analysis results, the median value of the TAM density was higher in the CC group (5,540.14) than in the CIN I–III group (2,502.17) and the chronic cervicitis group (1,403.31), with statistical significance in all three groups (P<0.001, for between-group comparisons). The number of neo-vessels was also much higher in the CC group (n=27) than in the CIN I–III group (n=17) or the chronic cervicitis group (n=6.5), with statistical significance in all three groups (P<0.001, for between-group comparisons). These findings demonstrated the great significance and close association of TAMs and tumor angiogenesis during CC development and progression. Thus, QDs-based in situ and simultaneous imaging of key cancer molecules may provide insights with regard to the biology of cancer invasion.
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