These authors contributed equally to this work.
Interaction of monocytes/macrophages with ovarian cancer cells promotes angiogenesis in vitro
Article first published online: 8 MAR 2013
© 2013 Japanese Cancer Association
Volume 104, Issue 4, pages 516–523, April 2013
How to Cite
(Cancer Sci 2013; 104: 516–523)
- Issue published online: 22 MAR 2013
- Article first published online: 8 MAR 2013
- Accepted manuscript online: 24 JAN 2013 12:35PM EST
- Manuscript Accepted: 11 JAN 2013
- Manuscript Revised: 6 JAN 2013
- Manuscript Received: 23 AUG 2012
- National Science Foundation of China. Grant Number: 81072136
- Shanghai Educational Committee. Grant Number: 09ZZ113
It has been established that macrophages and endothelial cells infiltrate peritoneum in the vicinity of tumor implants of epithelial ovarian cancer (EOC). This study investigates whether the interaction of ovarian cancer cells and tumor-associated macrophages could promote the involvement of endothelial cells in angiogenesis. Macrophage phenotypes were detected by fluorescence-activated cell sorting, and cytokine/chemokine secretion was measured by enzyme linked immunosorbent assay. The effect of co-culture of ovarian cancer cells and tumor-associated macrophage (TAM) cells on endothelial cell migration and tube formation was investigated. Signaling pathway mediators were also evaluated for their potential roles in endothelial cell activation by ovarian cancer cells co-cultured with TAM cells. Our results showed that higher expression of interleukin-8 (IL-8) expression associated with 54.26 ± 34.46% of TAM infiltration of peritoneum was significantly higher than 16.58 ± 17.74% of CD3+ T-cell by immunofluorescence co-staining and confocal microscopy. THP-1 cells exhibited M2-polarized phenotype markers with high proportion of CD68+, CD206+ and CD204+ markers after phorbol 12-myristate 13-acetate (PMA) treatment, After co-culturing with TAM cells in a transwell chamber system, EOC cells (SKOV3) increased their IL-8 expression at the level of mRNA and protein. After exposure to the conditioned medium obtained by co-culturing TAM and SKOV3 cells, the migration and tube formation of endothelial cells were enhanced significantly. Furthermore, the upregulation of IL-8 expression in ovarian cancer cells induced by macrophages could be inhibited by pyrollidine dithiocarbamate, an inhibitor of nuclear factor (NF)- κB signal pathway. We suggest that the interaction of ovarian cancer cells and tumor-associated macrophages enhances the ability of endothelial cells to promote the progression of ovarian cancer.