Effects of macrophage colony-stimulating factor on macrophage polarization, invasion and metastasis of ovarian cancer
10.13602/j.cnki.jcls.2019.07.08
- VernacularTitle:巨噬细胞集落刺激因子对巨噬细胞极化及卵巢癌细胞侵袭、转移的影响
- Author:
Weiyi WANG
1
;
Shanliang ZHONG
2
;
Linping YAN
1
;
Ji PANG
3
;
Miaolin ZHU
4
;
Jianhua ZHAO
2
Author Information
1. Department of Clinical Laboratory, the Affiliated Cancer Hospital of Nanjing Medical University/Jiangsu Cancer Hospital/Jiangsu Institute of Cancer Research
2. Center of Clinical Laboratory Science, the Affiliated Cancer Hospital of Nanjing Medical University/Jiangsu Cancer Hospital/Jiangsu Institute of Cancer Research
3. Department of Physiology, School of Medicine, Jiangsu University
4. Department of Pathology, the Affiliated Cancer Hospital of Nanjing Medical University/Jiangsu Cancer Hospital/Jiangsu Institute of Cancer Research
- Publication Type:Journal Article
- Keywords:
ovarian cancer;
macrophage colony-stimulating factor;
polarization;
M2 macrophage;
metastasis
- From:
Chinese Journal of Clinical Laboratory Science
2019;37(7):512-517
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effects of macrophage colony-stimulating factor (M-CSF) on the polarization and infiltration of M2 macrophages and the invasion and metastasis of tumor cells in ovarian cancer microenvironment.
Methods:A co-culture system consisting of ovarian cancer cells (A2780 and SKOV3) and THP-1 derived macrophages was established in vitro. The M-CSF levels in culture medium and M-CSF mRNA levels in cancer cells and macrophages were detected by ELISA and qRT-PCR, respectively. The proportion of CD68+CD163+ M2 macrophages (polarization cells) was determined by flow cytometry. The invasive and metastatic ability of A2780 and SKOV3 cells after co-culturing with M2 macrophages were analyzed using Transwell assay. The expression levels of M-CSF, CD68+, CD163+ and E-cad in paraffin sections of 52 patients with ovarian cancer and 18 patients with benign ovarian tumor were detected by the immunohistochemistry staining, and their correlations and the relationship between M-CSF and clinicopathological features of ovarian cancer patients were analyzed.
Results:The M-CSF levels in culture medium of the co-culture group (A2780 and SKOV3 cells co-cultured with M2 macrophages) were significantly higher than that of A2780 and SKOV3 cells alone (t=14.315 and 12.338, P＜0.01). Fluorescence quantitative PCR results showed that the increased M-CSF originated from the secretion of co-cultured ovarian cancer cells (t=29.915 and 36.826, P＜0.01). The proportions of CD68+CD163+ M2 macrophages in the A2780 cells co-cultured with M2 macrophages group and SKOV3 cells co-cultured with M2 macrophages group were (6.14±0.50)% and (7.32±0.67)%, respectively, which were significantly higher than that in the M2 macrophages alone group ([1.82±0.34]%, t=12.289 and 12.711, P＜0.01). Transwell assay showed that the co-culture environment enhanced the invasion of A2780 and SKOV3 cells (24.00±4.81 vs 75.20±6.42, t=11.058; 18.40±2.31 vs 61.60±9.66, t=7.537, P＜0.01). The expression levels of M-CSF in ovarian cancer tissues were positively correlated with the number of CD68+ cells and CD163+ cells (r=0.690 and 0.596, P＜0.01), and negatively with the expression levels of E-cad (r=-0.566, P＜0.01). Moreover, the expression levels of M-CSF and the number of CD68+ cells and CD163+ cells in ovarian cancer tissues were significantly higher than that in benign ovarian tumor tissues, however, the expression levels of E-cad were on the contrary. The expression levels of M-CSF in ovarian cancer tissues were significantly correlated with tumor stage, differentiation and lymphatic node metastasis (χ2=6.240, 6.612 and 4.544, respectively, P＜0.05).
Conclusion:The increased expression of M-CSF in ovarian cancer microenvironment may induce the polarization and infiltration of CD68+CD163+ M2 macrophages, and then promote the invasion and metastasis of ovarian cancer cells.
