Crosstalk between stromal, immune, and ovarian cancer cells in lipid-rich tumor microenvironment exhibits proliferative features

Figures

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  Figure 1. Lipid metabolic pathway alteration and crosstalk between ovarian cancer cells and adipocytes. (By Figdraw.) (a) Endogenous FAs de novo synthesis was elevated in ovarian cancer cells under the demand of original materials for higher FAO rate, membrane structure construction, and forming signaling factors, which facilitates tumor progression. (b) FAO correlated process was accelerated due to the over-expression of CPT1A, which is responsible for transporting fatty acyl-CoA from cytosol to mitochondrial matrix. (c) Lipids are first processed into storage form before being accumulated and stored in LDs. Correlating enzymes that turn FAs into TAGs have been found up-regulated in cancer cells, which is consistent with the fact that high LD accumulation is a type of stress response. (d) Cell membrane components consist of phospholipids, polyunsaturated FAs, and cholesterol to maintain the integrity and fluidity of membranes, which often relates to adhesion or metastasis of malignancies. (e) The crosstalk between ovarian cancer and adipocytes involves the secretion of pro-tumor factors and increased lipolysis of adipocytes, providing ovarian cancer cells with more FAs for FAO.

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  Figure 2. Interaction between stromal cells and immune cells in lipid-rich TME. (By Figdraw.) In the stromal TME, the interaction of cancerous, stromal, and immune cells tends to transform TME cells into a pro-tumor characteristic by secreting proliferative cytokines and lipid metabolites. Activation of lipolysis in adipocytes and adipokines secretion serve as energy resources and provide proliferative TME. Remodeling extracellular matrix completed by CAFs prepares cancer cells for metastasis, meanwhile inducing an immunosuppressive TME through secreting EVs and inhibiting CD8+ T cells’ immune response. Immune cells also exhibited enhancement in lipid metabolism, which results in immunosuppressive phenotypes, such as down-regulation of tumor-specific antigen presentation, increased anti-inflammatory signaling molecules, as well as increased M2-polarization of TAMs.