scholarly journals AXL Receptor in Cancer Metastasis and Drug Resistance: When Normal Functions Go Askew

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4864
Author(s):  
Almira Auyez ◽  
A. Emre Sayan ◽  
Marina Kriajevska ◽  
Eugene Tulchinsky
Keyword(s):  
Drug Resistance ◽  
Cancer Cells ◽  
Tyrosine Kinases ◽  
Cancer Metastasis ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Cell Activity ◽  
Tumour Microenvironment ◽  
Epithelial Cancers ◽  
Key Factor

The TAM proteins TYRO3, AXL, and MER are receptor tyrosine kinases implicated in the clearance of apoptotic debris and negative regulation of innate immune responses. AXL contributes to immunosuppression by terminating the Toll-like receptor signaling in dendritic cells, and suppressing natural killer cell activity. In recent years, AXL has been intensively studied in the context of cancer. Both molecules, the receptor, and its ligand GAS6, are commonly expressed in cancer cells, as well as stromal and infiltrating immune cells. In cancer cells, the activation of AXL signaling stimulates cell survival and increases migratory and invasive potential. In cells of the tumour microenvironment, AXL pathway potentiates immune evasion. AXL has been broadly implicated in the epithelial-mesenchymal plasticity of cancer cells, a key factor in drug resistance and metastasis. Several antibody-based and small molecule AXL inhibitors have been developed and used in preclinical studies. AXL inhibition in various mouse cancer models reduced metastatic spread and improved the survival of the animals. AXL inhibitors are currently being tested in several clinical trials as monotherapy or in combination with other drugs. Here, we give a brief overview of AXL structure and regulation and discuss the normal physiological functions of TAM receptors, focusing on AXL. We present a theory of how epithelial cancers exploit AXL signaling to resist cytotoxic insults, in order to disseminate and relapse.

scholarly journals Nature Exposure and Its Effects on Immune System Functioning: A Systematic Review

2021 ◽  
Vol 18 (4) ◽  
pp. 1416
Author(s):  
Liisa Andersen ◽  
Sus Sola Corazon ◽  
Ulrika Karlsson Stigsdotter
Keyword(s):  
Systematic Review ◽  
Natural Killer Cell Activity ◽  
Public Health Practice ◽  
Killer Cell ◽  
Cell Activity ◽  
Natural Environments ◽  
Comprehensive Overview ◽  
Potential Health ◽  
Positive Effects

Given the drastic changes in our lifestyles and ecosystems worldwide, the potential health effects of natural environments have grown into a highly pervasive topic. Recent scientific findings suggest beneficial effects from nature exposure on human immune responses. This review aims at providing a comprehensive overview of literature published on immunomodulatory effects of nature exposure by inhalation of natural substances. A systematic database search was performed in SCOPUS and PubMed. The quality and potential bias of included studies (n = 33) were assessed by applying the EPHPP (Effective Public Health Practice Project) tool for human studies and the ARRIVE (Animal Research: Reporting of In Vivo Experiments) and SYRCLE (Systematic Review Centre for Laboratory Animal Experimentation) tools for animal studies. The synthesis of reviewed studies points to positive effects of nature exposure on immunological health parameters; such as anti-inflammatory, anti-allergic, anti-asthmatic effects or increased NK (natural killer) cell activity. Decreased expression of pro-inflammatory molecules, infiltration of leukocytes and release of cytotoxic mediators are outcomes that may serve as a baseline for further studies. However, partially weak study designs evoked uncertainties about outcome reproducibility and key questions remain open concerning effect sizes, duration of exposure and contributions of specific vegetation or ecosystem types.

Acute electrical stimulation of lateral hypothalamus increases natural killer cell activity in rats

1996 ◽  
Vol 67 (1) ◽  
pp. 67-70 ◽  
Author(s):  
Marcus Wenner ◽  
Noriyuki Kawamura ◽  
Hitoshi Miyazawa ◽  
Yukihiro Ago ◽  
Toshio Ishikawa ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Natural Killer Cell ◽  
Natural Killer ◽  
Lateral Hypothalamus ◽  
Natural Killer Cell Activity ◽  
Killer Cell ◽  
Cell Activity ◽  
Killer Cell Activity ◽  
Stimulation Of

scholarly journals The metabolic adaptation mechanism of metastatic organotropism

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Chao Wang ◽  
Daya Luo
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Cancer Metabolism ◽  
Cancer Metastasis ◽  
Tumour Microenvironment ◽  
Metabolic Adaptation ◽  
Adaptation Mechanism ◽  
Metastatic Sites ◽  
The Impact

AbstractMetastasis is a complex multistep cascade of cancer cell extravasation and invasion, in which metabolism plays an important role. Recently, a metabolic adaptation mechanism of cancer metastasis has been proposed as an emerging model of the interaction between cancer cells and the host microenvironment, revealing a deep and extensive relationship between cancer metabolism and cancer metastasis. However, research on how the host microenvironment affects cancer metabolism is mostly limited to the impact of the local tumour microenvironment at the primary site. There are few studies on how differences between the primary and secondary microenvironments promote metabolic changes during cancer progression or how secondary microenvironments affect cancer cell metastasis preference. Hence, we discuss how cancer cells adapt to and colonize in the metabolic microenvironments of different metastatic sites to establish a metastatic organotropism phenotype. The mechanism is expected to accelerate the research of cancer metabolism in the secondary microenvironment, and provides theoretical support for the generation of innovative therapeutic targets for clinical metastatic diseases.

Lymphocyte subset distribution and natural killer cell activity in men with idiopathic hypogonadotropic hypogonadism

1991 ◽  
Vol 124 (4) ◽  
pp. 399-404 ◽  
Author(s):  
Wieland Kiess ◽  
Linda L. Liu ◽  
Nicholas R. Hall
Keyword(s):  
Natural Killer Cell ◽  
Natural Killer ◽  
Natural Killer Cell Activity ◽  
Hypogonadotropic Hypogonadism ◽  
Killer Cell ◽  
Cell Activity ◽  
Hormonal Treatment ◽  
Plasma Testosterone ◽  
Idiopathic Hypogonadotropic Hypogonadism ◽  
Testosterone Levels

Abstract. Sex-related differences in immune responsiveness are mediated at least in part by sex steroid hormones. Lymphocyte subset distribution in peripheral blood and natural killer cell function both have been reported to be under hormonal control. In order to gain more insight into sex steroid hormone action on the immune system, we have measured the lymphocyte subset distribution and natural killer cell activity in 18 men with idiopathic hypogonadotropic hypogonadism before treatment, and after hormonal treatment had normalized plasma testosterone levels. In untreated patients, the mean plasma testosterone concentrations were significantly lower than those in the treated men (3.0 ± 0.5 nmol/l vs 16 ± 1.7 nmol/l, p < 0.001). The percentage of peripheral CD3+ lymphocytes, CD8+ cells, the CD4+/CD8+ ratio, and the natural killer cell activity of peripheral mononuclear cells measured in a 51Cr release assay against target K 562 cells did not differ between patients with idiopathic hypogonadotropic hypogonadism and healthy adults, and most importantly, did not change during hormonal treatment which normalized plasma testosterone levels in the patients. In contrast, the percentage of peripheral CD4+ cells was significantly higher in untreated patients compared with normal adult subjects or patients with idiopathic hypogonadotropic hypogonadism after hormonal treatment that resulted in normal plasma testosterone levels (53 ± 2 vs 47 ± 2, p < 0.05). It should be noted that the percentage of peripheral CD 16+ cells was significantly lower in untreated men with low plasma testosterone levels than in normal controls. The percentage of CD16+ cells in peripheral venous blood rose significantly after hormonal treatment restored plasma testosterone levels to normal (6 ± 1 vs 11 ± 1, p < 0.001). In addition, the percentage of peripheral CD16+ cells correlated significantly with the plasma testosterone levels measured in men with idiopathic hypogonadotropic hypogonadism (r = 0.534, p < 0.001). In conclusion, both the percentage of peripheral CD4+ cells (T-helper lymphocytes) and peripheral CD16+ cells (non-T-non-B cells) are related to the plasma testosterone levels in men with idiopathic hypogonadotropic hypogonadism. These data suggest that in vivo human immune cells are under the regulatory influence of endogenous sex steroids.

Sign in / Sign up

Export Citation Format

Share Document