MAPK Signaling Is Required for Generation of Tunneling Nanotube-Like Structures in Ovarian Cancer Cells.
Jennifer M ColeRichard DahlKaren D Cowden DahlPublished in: Cancers (2021)
Ovarian cancer (OC) cells survive in the peritoneal cavity in a complex microenvironment composed of diverse cell types. The interaction between tumor cells and non-malignant cells is crucial to the success of the metastatic process. Macrophages activate pro-metastatic signaling pathways in ovarian cancer cells (OCCs), induce tumor angiogenesis, and orchestrate a tumor suppressive immune response by releasing anti-inflammatory cytokines. Understanding the interaction between immune cells and tumor cells will enhance our ability to combat tumor growth and dissemination. When co-cultured with OCCs, macrophages induce projections consistent with tunneling nanotubes (TnTs) to form between OCCs. TnTs mediate transfer of material between cells, thus promoting invasiveness, angiogenesis, proliferation, and/or therapy resistance. Macrophage induction of OCC TnTs occurs through a soluble mediator as macrophage-conditioned media potently induced TnT formation in OCCs. Additionally, EGFR-induced TnT formation in OCCs through MAPK signaling may occur. In particular, inhibition of ERK and RSK prevented EGFR-induced TnTs. TnT formation in response to macrophage-conditioned media or EGFR signaling required MAPK signaling. Collectively, these studies suggest that inhibition of ERK/RSK activity may dampen macrophage-OCC communication and be a promising therapeutic strategy.
Keyphrases
- signaling pathway
- induced apoptosis
- pi k akt
- small cell lung cancer
- cell cycle arrest
- high glucose
- oxidative stress
- endothelial cells
- immune response
- diabetic rats
- adipose tissue
- epidermal growth factor receptor
- squamous cell carcinoma
- tyrosine kinase
- endoplasmic reticulum stress
- stem cells
- cell proliferation
- drug induced
- single cell
- cell death
- vascular endothelial growth factor
- mass spectrometry
- cell therapy
- case control