Macrophages Promote Ovarian Cancer-Mesothelial Cell Adhesion by Upregulation of ITGA2 and VEGFC in Mesothelial Cells

• Published in: Cells (Basel, Switzerland) Vol. 12; no. 3; p. 384
• Main Authors: Cho, Seung-Kye, Lee, Kijun, Woo, Jeong-Hwa, Choi, Jung-Hye
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20.01.2023; MDPI
• Subjects: adhesion; AKT protein; Antibodies; Biotechnology; Cell adhesion; Cell adhesion & migration; Cell Adhesion - physiology; Cell Line, Tumor; Cytokines; Development and progression; Female; Genes; Health aspects; Humans; ITGA2; macrophage; Macrophages; Macrophages - metabolism; mesothelial cells; Mesothelium; Metastases; Metastasis; Monocyte chemoattractant protein 1; mRNA; Ovarian cancer; Ovarian Neoplasms - pathology; Proto-Oncogene Proteins c-akt - metabolism; Tumor Microenvironment; Up-Regulation - genetics; Vascular endothelial growth factor; Vascular Endothelial Growth Factor C - metabolism; VEGFC; South Korea; Canada; Grand Island New York; United States > US; VEGFC; macrophage; adhesion; mesothelial cells; ovarian cancer; ITGA2
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells12030384

Ovarian cancer is a metastatic disease that frequently exhibits extensive peritoneal dissemination. Recent studies have revealed that noncancerous cells inside the tumor microenvironment, such as macrophages and mesothelial cells, may play a role in ovarian cancer metastasis. In this study, we found that human ovarian cancer cells (A2780 and SKOV3) adhered more to human mesothelial Met5A cells stimulated by macrophages (M-Met5A) in comparison to unstimulated control Met5A cells. The mRNA sequencing revealed that 94 adhesion-related genes, including , , , and were markedly upregulated in M-Met5A cells. Knockdown of ITGA2 and VEGFC in M-Met5A cells significantly inhibited the adhesion of ovarian cancer cells. Inhibition of the JNK and Akt signaling pathways suppressed ITGA2 and VEGFC expression in M-Met5A cells as well as ovarian cancer-mesothelial cell adhesion. Furthermore, increased production of CC chemokine ligand 2 (CCL2) and CCL5 by macrophages elevated ovarian cancer-mesothelial cell adhesion. These findings imply that macrophages may play a significant role in ovarian cancer-mesothelial cell adhesion by inducing the mesothelial expression of adhesion-related genes via the JNK and Akt pathways.