Thrombospondin-1 interactions regulate eicosanoid metabolism and signaling in cancer-related inflammation

Abstract

The metabolism of arachidonic acid and other polyunsaturated fatty acids produces eicosanoids, a family of biologically active lipids that are implicated in homeostasis and in several pathologies that involve inflammation. Inflammatory processes mediated by eicosanoids promote carcinogenesis by exerting direct effects on cancer cells and by affecting the tumor microenvironment. Therefore, understanding how eicosanoids mediate cancer progression may lead to better approaches and chemopreventive strategies for the treatment of cancer. The matricellular protein thrombospondin-1 is involved in processes that profoundly regulate inflammatory pathways that contribute to carcinogenesis and metastatic spread. This review focuses on interactions of thrombospondin-1 and eicosanoids in the microenvironment that promote carcinogenesis and how the microenvironment can be targeted for cancer prevention to increase curative responses of cancer patients.

Signaling lipids as diagnostic biomarkers for ocular surface cicatrizing conjunctivitis

“…Considering the inflammatory nature of ocular MMP, it is reasonable to assume that inflammatory metabolites may be actively involved, which justifies the use of a metabolomics-based approach to elucidate their roles in the onset and progression of ocular MMP. More specifically, signaling lipid mediators are bioactive lipids and lipid derivatives that mediate a variety of biological signaling events including proinflammatory, anti-inflammatory, or pro-resolving [21][22][23]. Metabolomics-based approaches targeting signaling lipid mediators are expected to significantly contribute to revealing inflammatory processes related to ocular MMP as well as potential disease biomarkers.…”

Effect of THBS1 on the Biological Function of Hypertrophic Scar Fibroblasts

“…THBS1 is also known to be involved in the regulation of multiple signalling pathways [ 28 , 29 ] and antagonize VEGF in several important ways: inhibiting its release from the ECM, direct interaction, and inhibiting signal transduction [ 30 – 32 ]. The very low-density lipoprotein receptor inside the membrane of capillary endothelial cells binds TSP-1 and mediates the inhibition of cell cycle progression via the Akt/MAPK pathway [ 33 ]; therefore, targeting the TSP-1/CD47/NO signalling axis may promote the healing of skin grafts [ 30 ].…”

GGPP depletion initiates metaflammation through disequilibrating CYB5R3-dependent eicosanoid metabolism

“…The ER-resident CYB5R3 serves to maintain ER oxidation/reduction balance necessary for such eicosanoids synthesis as microsomal metabolism, or directly participate the metabolic reactions. When MVA pathway is inhibited, CYB5R3 prenylation was ablated and the bioactive intermediate metabolites or substrates of eicosanoid metabolism were accumulated, resulting in metaflammation and death (31,(33)(34)(35).…”

“…S4). As eicosanoids are closely related to inflammatory responses (31)(32)(33)(34)(35)(36), the metaflammation occurring in the mutant cells may be primarily contributed by the abnormal eicosanoids production.…”