Angiogenic Properties of NK Cells in Cancer and Other Angiogenesis-Dependent Diseases

Abstract

The pathogenesis of many serious diseases, including cancer, is closely related to disturbances in the angiogenesis process. Angiogenesis is essential for the progression of tumor growth and metastasis. The tumor microenvironment (TME) has immunosuppressive properties, which contribute to tumor expansion and angiogenesis. Similarly, the uterine microenvironment (UME) exerts a tolerogenic (immunosuppressive) and proangiogenic effect on its cells, promoting implantation and development of the embryo and placenta. In the TME and UME natural killer (NK) cells, which otherwise are capable of killing target cells autonomously, enter a state of reduced cytotoxicity or anergy. Both TME and UME are rich with factors (e.g., TGF-β, glycodelin, hypoxia), which support a conversion of NK cells to the low/non-cytotoxic, proangiogenic CD56brightCD16low phenotype. It is plausible that the phenomenon of acquiring proangiogenic and low cytotoxic features by NK cells is not only limited to cancer but is a common feature of different angiogenesis-dependent diseases (ADDs). In this review, we will discuss the role of NK cells in angiogenesis disturbances associated with cancer and other selected ADDs. Expanding the knowledge of the mechanisms responsible for angiogenesis and its disorders contributes to a better understanding of ADDs and may have therapeutic implications.

miR-150-5p-Containing Extracellular Vesicles Are a New Immunoregulator That Favor the Progression of Lung Cancer in Hypoxic Microenvironments by Altering the Phenotype of NK Cells

“…CD56 bright CD16 − cells have also been identified as the predominant tumor subset of NK cells in lung cancer [ 39 ]. The major factors contributing to peripheral blood NK-cell phenotype remodeling are TGF-β, glycodelin-A (GdA), prostaglandin E2 (PGE2), and hypoxia [ 40 ]. Our results showed that hypoxic lung cancer-derived EVs increased the polarization of NK cells to dNK-like cells with pro-angiogenic phenotypes, which have the ability to support angiogenesis in vitro with several soluble factors including, VEGF, CXCL1/2 and IL-8.…”

“…We therefore use the term “EVs” in the current report. Indeed, a variety of isolation methods based on different principles, such as ultracentrifugation, density gradient, precipitation, immune precipitation, membrane affinity, size-exclusion chromatography, iodixanol gradient and phosphatidylserine affinity, are available [ 40 , 57 ]. Different isolation methods yielded EVs with different profiles in terms of morphology, particle size, and content.…”

A History of Endometriosis Is Associated With Decreased Peripheral NK Cytotoxicity and Increased Infiltration of Uterine CD68+ Macrophages

“…Circulating NK cytotoxicity might be regulated by other factors, such as other surface receptors (NKp44, NKG2A, ITAM-KIR, etc. ), the production of IFN-g and TNF-a, NK cell maturation and development, proangiogenic features of NK cells, or the interaction with other immune cells such as regulatory T cells (34)(35)(36)(37)(38). It is worth noting that, although PBMC cytotoxicity is used to represent NK cytotoxicity in many studies, peripheral T cells might also exhibit cytotoxicity via the production of cytokines, such as IFN-g, TNF-a, and the human cytotoxic factor (39,40).…”

The Multifaceted Role of Curcumin in Advanced Nanocurcumin Form in the Treatment and Management of Chronic Disorders

“…Antigens are the most frequent neurotransmitter medicines, while receptor tyrosine kinase agents are the most common direct amplifiers of VEGF activity. Curcumin inhibited VEGF and angiopoietin 1 and 2 gene production in EAT cells, VEGF and angiopoietin one oxidative stress in NIH3T3 cells, and KDR gene expression in HUVEC cells in a time-dependent manner [ 96 ]. Curcumin shown to inhibit VEGF production in blood clotting via mechanisms such as TGF release, COX-2 hypertrophy, hydrogen peroxide discharge, conventional and aberrant EGFR, Src signaling, and abnormal NF-B signaling [ 97 ].…”