Matrix Metalloproteinases’ Role in Tumor Microenvironment

González-Ávila, Georgina; Sommer, Bettina; García-Hernández, Alejandra; Ramos, Carlos

doi:10.1007/978-3-030-40146-7_5

Cited by 76 publications

(71 citation statements)

References 214 publications

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“…LOX family genes have been shown to play key roles in the formation and remodeling of ECM, which could affect biological processes such as cell differentiation, proliferation, adhesion, morphogenesis and phenotypic expression. 31,32 Finally, we found that LOX and LOXL2 were significantly upregulated and predicted poor survival in KIRC. Furthermore, enrichment analyses of LOX, LOXL2 and their co-expressed genes revealed that they were closely correlated with extracellular matrix, extracellular space and ECM structuration.…”

Section: Discussionmentioning

confidence: 66%

Comprehensive analysis on the expression levels and prognostic values of LOX family genes in kidney renal clear cell carcinoma

Lin

Zheng

et al. 2020

Cancer Medicine

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Section: Discussionmentioning

confidence: 66%

Comprehensive analysis on the expression levels and prognostic values of LOX family genes in kidney renal clear cell carcinoma

Lin

Zheng

et al. 2020

Cancer Medicine

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“…Webber et al [44] Prostate, bladder, colorectal and breast cancer cell lines TGF-β Differentiation of fibroblasts to myofibroblasts Hong et al [45] Acute myeloid leukemia TGF-β Immunosuppression Zheng et al [46] Tumor-associated macrophages Apolipoprotein-E Migration of gastric cancer cells Shi et al [47] Gastric cancer cells STAT3 PD-L1 expression on neutrophils to suppress T-cell-mediated immunity…”

Section: Glioblastoma Progressionmentioning

confidence: 99%

“…Recent studies reported a functional role for miRNA-containing sEVs derived from M2-like macrophages in regulating migration and invasion of colorectal cancer cells [69]. Another study demonstrated the sEV-mediated transfer of functional apolipoprotein E from TAMs to tumor cells, resulting in an enhanced migration of gastric cancer cells [46]. Arginase-1(+) sEVs derived from TAMs promoted tumor cell migration and proliferation in glioblastoma and were considered as a distributor of proteins with pro-tumor functions in the TME [43].…”

Section: Effects Of Tex On Macrophagesmentioning

confidence: 99%

Potential Roles of Tumor Cell- and Stroma Cell-Derived Small Extracellular Vesicles in Promoting a Pro-Angiogenic Tumor Microenvironment

Ludwig

Rubenich

Zaręba

et al. 2020

Cancers

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Extracellular vesicles (EVs) are produced and released by all cells and are present in all body fluids. They exist in a variety of sizes, however, small extracellular vesicles (sEVs), the EV subset with a size range from 30 to 150 nm, are of current interest. They are characterized by a distinct biogenesis and complex cargo composition, which reflects the cytosolic contents and cell-surface molecules of the parent cells. This cargo consists of proteins, nucleic acids, and lipids and is competent in inducing signaling cascades in recipient cells after surface interactions or in initiating the generation of a functional protein by delivering nucleic acids. Based on these characteristics, sEVs are now considered as important mediators of intercellular communication. One hallmark of sEVs is the promotion of angiogenesis. It was shown that sEVs interact with endothelial cells (ECs) and promote an angiogenic phenotype, ultimately leading to increased vascularization of solid tumors and disease progression. It was also shown that sEVs reprogram cells in the tumor microenvironment (TME) and act in a functionally cooperative fashion to promote angiogenesis by a paracrine mechanism involving the differential expression and secretion of angiogenic factors from other cell types. In this review, we will focus on the distinct functions of tumor-cell-derived sEVs (TEX) in promotion of angiogenesis and describe their potential as a therapeutic target for anti-angiogenic therapies. Also, we will focus on non-cancer stroma-cell-derived small extracellular vesicles and their potential role in stimulating a pro-angiogenic TME.

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“…MMPs can be grouped into collagenases, gelatinases, matrilysins, stromelysins, glycosylphosphatidylinositol-anchored MMPs, transmembrane type I and II MMPs, and other MMPs, based on substrate specificity and structural organization. MMPs are synthesized as inactive zymogens (pro-MMPs) and their activation involves the proteolytic cleavage either by trypsin, other MMPs, plasmin, by allosteric activation, or by chemical modification elicited for example by reactive oxygen species (ROS); followed by the autocatalytic removal of the pro-peptide [10].…”

Section: Introductionmentioning

confidence: 99%

Investigating Glioblastoma Response to Hypoxia

et al. 2020

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Glioblastoma (GB) is the most common and deadly type of primary malignant brain tumor with an average patient survival of only 15–17 months. GBs typically have hypoxic regions associated with aggressiveness and chemoresistance. Using patient derived GB cells, we characterized how GB responds to hypoxia. We noted a hypoxia-dependent glycolytic switch characterized by the up-regulation of HK2, PFKFB3, PFKFB4, LDHA, PDK1, SLC2A1/GLUT-1, CA9/CAIX, and SLC16A3/MCT-4. Moreover, many proangiogenic genes and proteins, including VEGFA, VEGFC, VEGFD, PGF/PlGF, ADM, ANGPTL4, and SERPINE1/PAI-1 were up-regulated during hypoxia. We detected the hypoxic induction of invasion proteins, including the plasminogen receptor, S100A10, and the urokinase plasminogen activator receptor, uPAR. Furthermore, we observed a hypoxia-dependent up-regulation of the autophagy genes, BNIP-3 and DDIT4 and of the multi-functional protein, NDRG1 associated with GB chemoresistance; and down-regulation of EGR1 and TFRC (Graphical abstract). Analysis of GB patient cohorts’ revealed differential expression of these genes in patient samples (except SLC16A3) compared to non-neoplastic brain tissue. High expression of SLC2A1, LDHA, PDK1, PFKFB4, HK2, VEGFA, SERPINE1, TFRC, and ADM was associated with significantly lower overall survival. Together these data provide important information regarding GB response to hypoxia which could support the development of more effective treatments for GB patients.

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Matrix Metalloproteinases’ Role in Tumor Microenvironment

Cited by 76 publications

References 214 publications

Comprehensive analysis on the expression levels and prognostic values of LOX family genes in kidney renal clear cell carcinoma

Comprehensive analysis on the expression levels and prognostic values of LOX family genes in kidney renal clear cell carcinoma

Potential Roles of Tumor Cell- and Stroma Cell-Derived Small Extracellular Vesicles in Promoting a Pro-Angiogenic Tumor Microenvironment

Investigating Glioblastoma Response to Hypoxia

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