Interaction of monocytes/macrophages with ovarian cancer cells promotes angiogenesis in vitro

Abstract

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)-jB 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. (Cancer Sci 2013; 104: 516-523) E pithelial ovarian cancer (EOC) accounts for 90% of all ovarian cancers and has become the leading cause of death from gynecological cancers in North America and Europe.(1)A remarkable feature of advanced EOC is the presence of widespread peritoneal metastases at the time of the initial diagnosis. However, the mechanisms of peritoneal seeding, spreading and progression remain elusive.Tumor microenvironment consists of various stromal cells, including activated endothelial cells, tumor-associated macrophages (TAMs), fibroblasts, and bone marrow-derived cells.(2)Our previous study has confirmed that more than 75% of mononuclear immune cells in peritoneum close to a tumor implant were TAM, which mimic chronic inflammation. Most studies reported that infiltrating TAMs were associated with cancer progression.(4-7) Tumor-associated macrophages might be recruited from peripheral blood by chemokines and then positioned in the tumor stroma. Those macrophages could be 'educated' and differentiated into M1 or M2 forms as a result of activation by some molecular factors. Interferon-c (IFN-c)

Suppression of endothelial cell migration by tumor associated macrophage-derived exosomes is reversed by epithelial ovarian cancer exosomal lncRNA

“…Our previous work suggested that the co-culture of tumor-associated macrophage supernatant with EOCs could promote endothelial cell migration [3]. Here, we further showed that exosomes secreted from TAMs in the absence of EOC stimulation could suppress the migration of endothelial cells.…”

Cross‐talk between ovarian cancer cells and macrophages through periostin promotes macrophage recruitment

“…Increasing evidence has shown that the interactions between tumor cells and infiltrated macrophages create a tumor‐supportive microenvironment . High levels of POSTN accumulate in ascites from ovarian cancer patients.…”

“…Increasing evidence has shown that the interactions between tumor cells and infiltrated macrophages create a tumor-supportive microenvironment. 32,33 High levels of POSTN accumulate in ascites F I G U R E 5 THP-1-derived macrophages were recruited by periostin (POSTN) by A2780 cell conditioned medium (CM). A, Representative images of THP-1-derived macrophages (Mφ) migrating to A2780 cell-derived CM.…”

Effect of Th1/Th2 cytokine administration on proinflammatory SKOV-3 cell activation

“…Also immune cells and mesenchymal cells can interact with malignant cells. Wang et al [41] showed that the cross talk between ovarian cancer cells and tumor-associated macrophages enhances the ability of endothelial cells to promote the progression of ovarian cancer. Moreover, Lis et al [42] demonstrated that co-culture of ovarian cancer cells in direct cellular contact with mesenchymal stem cells induces broad transcriptomic changes related to cellular adhesion, invasion, migration, proliferation and chemoresistance.…”