The main group of enzymes responsible for the collagen and other protein degradation in extracellular matrix (ECM) are matrix metalloproteinases (MMPs) . Matrix metalloproteinases (MMPs) are a large family of calcium-dependent zinc-containing endopeptidases, which are responsible for the tissue remodeling and degradation of the extracellular matrix (ECM), including collagens, elastins, gelatin, matrix glycoproteins, and proteoglycan . MMP family can be divided into six groups: collagenases, gelatinases, stromelysins, matrilysins, membrane-type MMPs, and other non-classified MMPs . The MMPs are involved in many biologic processes, such as, tissue repair and remodulation, cellular differentiation, embryogenesis, morphogenesis , cell mobility, angiogenesis, cell proliferation and migration, wound healing, apoptosis. The deregulation of MMPs activity leads to development of numerous diseases [1, 4].
- August 6, 2021
Among the multiple immune cells, macrophages plays an important role throughout the tumor progression process. They are converted into tumor-associated macrophages (TAMs) when they are recruited into the tumor microenvironment. Induced by different microenvironmental signals, macrophages would polarize into two functional phenotypes, classically activated macrophages (M1) and alternatively activated macrophages (M2). M2 macrophages are often further subdivided into M2a, M2b, M2c, and M2d based on phenotypic variations.
- July 13, 2021
Extracellular Vesicles and particles (EVPs), including exosomes, are membrane-bound cargos (size range 30-150 nm) comprised of a lipid bilayer that contain various biomolecules, such as proteins or nucleic acids, and play crucial roles in different cellular or pathological processes. With increasing recognition of the central role of exosomes in intercellular (cell-to-cell) communication and transportation, current exosome research covers almost all research areas in biomedical science (immunology, neuroscience, oncology, endocrinology, and cardiovascular research) and have the great potential in both diagnosis (some of contained proteins or nucleic acids in exosomes can serve as biomarkers of diseases) and therapy (engineered exosomes can serve as new drug delivery system with high efficiency and low risks). Based on one latest study published on Cell (Hoshino et al., 2020, Cell 182, 1-18. https://doi.org/10.1016/j.cell.2020.07.009), tens of new pan-EVP markers and tumor-derived EVP markers in human tissues and plasma EVP proteins have been identified and can be useful for cancer detection and cancer type determination. This study greatly move the clinical application of exosomes forward in cancer diagnosis.
- July 6, 2021
Hypoxia and Angiogensis represent an important cellular player in the tumor microenvironment. Cancer cells are frequently surrounded by hypoxic microenvironment and, to survive, they have evolved multiple adaptations. One of the hallmark adaptations for cancer cells is the rewired metabolism, which is so-called tumor metabolic reprogramming, resulting in neoangiogenesis, metastasis, and immune evasion. Several hypoxia-responsive molecular determinants, such as hypoxia-inducible factors (HIFs), guide the cellular adaptation to hypoxia by gene activation. HIFs promotes vessel growth by upregulating multiple pro-angiogenic factors such as growth factors, cytokines, chemokines and ECM remodeling MMPs that mediate key aspects of endothelial, stromal, and vascular support cell biology.
- June 27, 2021
A new form of cell death, ferroptosis, was recently discovered. Ferroptosis is an iron-dependent programmed cell death resulting from alterations of metabolic processes and accumulation of lipid peroxidation that is toxic and damaging to the membrane structure. Ferroptosis initiation and execution lies at the intersection of amino acid, lipid, and iron metabolism, but ferroptosis sensitivity is also modulated by several lines of mechanisms, including A) the regulation of GSH and redox homeostasis, such as function of system Xc-, GPX4 regulation, FSP1-CoQ10- NAD(P)H pathway, sulfur transfer pathway, mevalonate (MVA) pathway, glutamine metabolic pathway, NRF2 and p53 regulatory axis; B) the regulation of iron homeostasis, such as the regulation of ATG5-ATG7-NCOA4 pathway, IREB regulation system, and the regulatory pathways of heatshock proteins; C) related enzymes around glucose and lipid metabolism, such as PHGDH, G6PD, ACSL4, and LPCAT3, etc. ; D) mitochondria function regulation, such as VDAC, mitochondrial electron transport chain (ETC) , TCA cycle and glutaminolysis.
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