title: Co-evolution of tumor-associated macrophages and tumor neo-vessels during cervical cancer invasion.
abstract: 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-componentin situimaging 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-basedin situand simultaneous imaging of key cancer molecules may provide insights with regard to the biology of cancer invasion.
authors.affiliation: Department of Breast Surgery, Changzhou Maternal and Child Health Care Hospital, Changzhou, Jiangsu 213003, P.R. China.
authors.forename: Shuting
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Pathology, Wuhan Center Hospital, Wuhan, Hubei 430014, P.R. China.
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Fang
authors.affiliation: Department of Oncology, Hunan Aerospace Hospital, Changsha, Hunan 410205, P.R. China.
authors.forename: Xianglang
authors.initials: X
authors.lastname: Li
authors.affiliation: Medical College of Wuhan University of Science and Technology, Wuhan, Hubei 430065, P.R. China.
authors.forename: Xiuxue
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Jingping
authors.initials: J
authors.lastname: Yuan
keywords: cervival cancer; quantum dots; tumor neo-vessels; tumor-associated macrophages