Triumph and tumult of matrix metalloproteinases and their crosstalk with eicosanoids in cancer

Abstract

Cancer development and metastasis are associated to perturbation in metabolic functions of tumor cells and surrounding inflammatory and stromal cell responses. Eicosanoids and lipid mediators, in this regard, attract potential attention during cancer development. Eicosanoids, which include prostaglandin, prostacyclin, thromboxane, and leukotriene, are synthesized from arachidonic acid when cells are stimulated by stress, cytokines, or other growth factors. However, the underlying mechanism of eicosanoids in cancer development, specially their interactions with proto-oncogene factors in tumor microenvironment, remain unexplored. On the other hand, matrix metalloproteinases (MMPs) are a group of zinc-dependent endopeptidases which are involved in degradation of different extracellular matrix (ECM) proteins. MMPs are associated with different physiological responses, including embryogenesis, vasculogenesis, and cellular remodeling, as well as different disease pathogenesis. Induced MMP responses are especially associated with cancer metastasis and secondary tumor development through proteolytic cleavage of several ECM and non-ECM proteins. Although both eicosanoids and MMPs are involved with cancer progression and metastasis, the interrelation between these two molecules are less explored. The present review discusses relevant studies that connect eicosanoids and MMPs and highlight the crosstalk between them offering novel therapeutic approach in cancer treatment.

Targeting the Nerve Growth Factor Signaling Impairs the Proliferative and Migratory Phenotype of Triple-Negative Breast Cancer Cells

“…The release of matrix metalloproteinases (MMPs) is crucial for ECM remodeling, cell invasion, and tumor progression ( Bonnans et al, 2014 ; Chatterjee et al, 2018 ; Yuzhalin et al, 2018 ). Since NGF induces MMP-9 release ( Khan et al, 2002 ), we analyzed the effect of NGF on MMP-9 release by MDA-MB-231 cells.…”

Novel Applications of NSAIDs: Insight and Future Perspectives in Cardiovascular, Neurodegenerative, Diabetes and Cancer Disease Therapy

“…Evidence from non-clinical trials indicates that eicosanoids and lipid mediators may are involved in cancer development surrounding inflammatory and stromal cell responses [ 43 ] and provides a reference for the potential benefits of NSAIDs in cancer chemotherapy via activation apoptosis [ 44 ] and modulation tumor autophagy through the PI3K/Akt/mTOR, MAPK/ERK1/2, P53/DRAM, AMPK/mTOR, Bip/GRP78, CHOP/GADD153 , and HGF/MET signaling pathways and inhibition lysosome function, leading to p53-dependent G1 cell-cycle arrest [ 45 ].…”

“…Data from new preclinical studies, scientific and technological developments in the 21st century have stimulated research and clinical trials of NSAIDs, which have been commonly used to control inflammation, pain, and fever over the last few centuries, for new NSAIDs therapeutic targets never used before, including neurodegenerative disorders, psychiatric, epilepsy, cardiovascular, diabetes and cancer [ 43 , 46 , 47 , 48 , 49 , 50 ].…”

Hold on or Cut? Integrin- and MMP-Mediated Cell–Matrix Interactions in the Tumor Microenvironment

“…To prevent accidental proteolysis, the gene expression of MMPs is strictly controlled at intracellular and extracellular levels by cell-matrix and intercellular interactions and the input of various growth factors, glucocorticoids, cytokines, retinoic acid, interleukins and eicosanoids [169,170]. All of these factors induce the expression of MMPs via, for example, NFκB, MAPK and JAK/STAT signaling ( [171] and references therein).…”