scholarly journals Interplay Between LOX Enzymes and Integrins in the Tumor Microenvironment

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 729 ◽  
Author(s):  
Pier Giorgio Amendola ◽  
Raphael Reuten ◽  
Janine Terra Erler
Keyword(s):  
Tumor Microenvironment ◽  
Structural Integrity ◽  
Lysyl Oxidase ◽  
Review Article ◽  
Amine Oxidases ◽  
Covalent Crosslinking ◽  
Cancer Types ◽  
Lox Inhibitors ◽  
Cell Phenotypes

Members of the lysyl oxidase (LOX) family are secreted copper-dependent amine oxidases that catalyze the covalent crosslinking of collagens and elastin in the extracellular matrix (ECM), an essential process for the structural integrity of all tissues. LOX enzymes can also remodel the tumor microenvironment and have been implicated in all stages of tumor initiation and progression of many cancer types. Changes in the ECM can influence several cancer cell phenotypes. Integrin adhesion complexes (IACs) physically connect cells with their microenvironment. This review article summarizes the main findings on the role of LOX proteins in modulating the tumor microenvironment, with a particular focus on how ECM changes are integrated by IACs to modulate cells behavior. Finally, we discuss how the development of selective LOX inhibitors may lead to novel and effective therapies in cancer treatment.

scholarly journals The Role of Extracellular Vesicles in the Development of a Cancer Stem Cell Microenvironment Niche and Potential Therapeutic Targets

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2435
Author(s):  
Thomas J. Brown ◽  
Victoria James
Keyword(s):  
Systematic Review ◽  
Tumor Microenvironment ◽  
Extracellular Vesicles ◽  
Multiple Cancer ◽  
Therapeutic Targeting ◽  
Small Component ◽  
Facilitated Communication ◽  
Cell Microenvironment ◽  
Cancer Types

Cancer stem cells (CSCs) have increasingly been shown to be a crucial element of heterogenous tumors. Although a relatively small component of the population, they increase the resistance to treatment and the likelihood of recurrence. In recent years, it has been shown, across multiple cancer types (e.g., colorectal, breast and prostate), that reciprocal communication between cancer and the microenvironment exists, which is, in part, facilitated by extracellular vesicles (EVs). However, the mechanisms of this method of communication and its influence on CSC populations is less well-understood. Therefore, the aim of this systematic review is to determine the evidence that supports the role of EVs in the manipulation of the tumor microenvironment to promote the survival of CSCs. Embase and PubMed were used to identify all studies on the topic, which were screened using PRISMA guidelines, resulting in the inclusion of 16 studies. These 16 studies reported on the EV content, pathways altered by EVs and therapeutic targeting of CSC through EV-mediated changes to the microenvironment. In conclusion, these studies demonstrated the role of EV-facilitated communication in maintaining CSCs via manipulation of the tumor microenvironment, demonstrating the potential of creating therapeutics to target CSCs. However, further works are needed to fully understand the targetable mechanisms upon which future therapeutics can be based.

scholarly journals Pan-Cancer Prognostic, Immunity, Stemness, and Anticancer Drug Sensitivity Characterization of N6-Methyladenosine RNA Modification Regulators in Human Cancers

2021 ◽  
Vol 8 ◽  
Author(s):  
Rui Li ◽  
Yun-Hong Yin ◽  
Xiu-Li Ji ◽  
Xiao Liu ◽  
Jian-Ping Li ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Anticancer Drug ◽  
Drug Sensitivity ◽  
Rna Modification ◽  
Immune Microenvironment ◽  
Normal Tissues ◽  
Tumor Immune Microenvironment ◽  
Cancer Types ◽  
Pan Cancer

N6-methyladenosine RNA modification plays a significant role in the progression of multiple tumorigenesis. Our study identified the imperative role of m6A regulators in the tumor immune microenvironment, survival, stemness score, and anticancer drug sensitivity of pan-cancer. The Wilcox test was to identify the differential expression between 17 m6A regulators across 33 TCGA cancer types and their normal tissues from UCSC Xena GDC pan-cancer. Survival analysis of m6A-related regulators in 33 TCGA cancer types was identified using the “survival” and “survminer” package. The Spearman correlation test and Pearson correlation test were used to identify the correlation relationship between m6A regulators expression and tumor microenvironment, tumor stem cell score, and drug sensitivity of anticancer drugs. ConsensusPathDB was used for exploring m6A regulators functional enrichment. The 17 (METTL3, WTAP, METTL14, RBM15, RBM15B, VIRMA, HNRNPC, HNRNPA2B1, YTHDC1, ZC3H13, YTHDF1, YTHDC2, YTHDF2, IGF2BP3, IGF2BP1, FTO, and ALKBH5) m6A regulators were differentially expressed in 18 TCGA cancer types and adjacent normal tissues. Correlation analysis indicated that the relationship between the expression of 17 m6A regulators and tumor microenvironment indicated that the higher expression of m6A regulators, the higher the degree of tumor stem cells. The anticancer drug sensitivity analysis indicated that ZC3H13 expression had a positive relationship with anticancer drugs such as selumetinib, dabrafenib, cobimetinib, trametinib, and hypothemycin (p < 0.001). YTHDF2 expression was significantly negatively correlated with the anticancer drug dasatinib (p < 0.001). The pan-cancer immune subtype analysis showed that the 17 m6A regulators were significantly different in immune subtype C1 (wound healing), C3 (inflammatory), C2 (IFN-gamma dominant), C5 (immunological quiet), C4 (lymphocyte depleted), and C6 (TGF-beta dominant) (p < 0.001). Our study provides a comprehensive insight for revealing the significant role of m6A regulators in the tumor immune microenvironment, stemness score, and anticancer drug sensitivity of human cancers.

Abstract 108: Deletion of Lrp1 In SMCS Differentially Alters Susceptibility of Distinct Vascular Beds to BAPN-Induced Aneurysm and Dissection Formation

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Areck A Ucuzian ◽  
Selen C Catania ◽  
Subhradip Mukhopadhyay ◽  
Rajabrata Sarkar ◽  
Dudley S Strickland
Keyword(s):  
Structural Integrity ◽  
Lysyl Oxidase ◽  
Ldl Receptor ◽  
Wild Type ◽  
Radiographic Evidence ◽  
Iliac Arteries ◽  
Aortic Aneurysm And Dissection ◽  
Genetic Deletion ◽  
Vascular Beds

Lysyl oxidase (LOX) inhibition by β-aminopropionitrile (BAPN) induces aortic aneurysm and dissection (AD). The LDL receptor-related protein 1 (LRP1) is an endocytic receptor that plays a key role in maintaining the structural integrity of vessels. Deletion of LRP1 in vascular smooth muscle cells (smLRP1 -/-) in mice induces fully penetrant and spontaneous aneurysms with aging. The objective of this study was to investigate the role of smLRP1 in modulating the susceptibility of various vascular beds to BAPN-induced AD. Wild-type (WT) and smLRP1 -/- mice were treated with BAPN supplemented in drinking water (3g/L). After 4-16 weeks, the vessels were analyzed histologically and with micro-CT. Abnormal elastic lamellae were identified throughout the vasculature of both the BAPN-treated WT and smLRP1 -/- cohorts. smLRP1 -/- mice were more susceptible to aneurysm formation after 8 (p=0.035) or 16 weeks (p=0.043) of treatment. Aneurysms in BAPN-treated WT mice were localized to the aorta, while aneurysms in BAPN-treated smLRP1 -/- mice were localized to the visceral and iliac arteries (Table). Histologic and radiographic evidence of AD was detected in the ascending and descending thoracic aorta in BAPN and AngII (subcutaneous,1μg/kg/min, 24 hrs)-treated WT mice, but not in BAPN and Ang II-treated smLRP1 -/- mice (Figure). Thoracic ruptures were more prevalent in the BAPN-treated WT group and abdominal ruptures were more prevalent in the BAPN-treated smLRP1 -/-group (p=0.02). In summary, these data demonstrate that genetic deletion of LRP1 in SMCs differentially alters the susceptibility of distinct vascular beds to the development of aneurysm and dissection upon LOX inhibition.

The role of Lysyl oxidase in tumor microenvironment of primary liver cancer

2018 ◽  
Vol 68 ◽  
pp. S675
Author(s):  
M. Lewinska ◽  
M.J. Perugorria ◽  
J. Banales ◽  
J. Andersen
Keyword(s):  
Tumor Microenvironment ◽  
Liver Cancer ◽  
Lysyl Oxidase ◽  
Primary Liver Cancer

Population Control (Review Article)

1961 ◽  
Vol 1 (3) ◽  
pp. 89-98
Author(s):  
Karol J. Krotki
Keyword(s):  
Population Control ◽  
Review Article ◽  
Small Enterprise ◽  
Opportunity Costs ◽  
Relative Importance ◽  
Factual Information ◽  
Undue Influence ◽  
Clear Cut ◽  
Economic Considerations

Discussions about the role of small enterprise in economic development tend to remain inconclusive partly because of the difficulty of assessing the relative importance of economic and non-economic objectives and partly because of the dearth of factual information on which to base an economic calculus. It is probably true, moreover, that, because of a lack of general agreement as to the economic case for or against small enterprise, non-economic considerations, including some merely romantic attitudes toward smallness and bigness, tend to exert an undue influence on public policies. There may, of course, be no clear-cut economic case. And noneconomic considerations should and will inevitably weigh significantly in policy decisions. If, however, some of the economic questions could be settled by more and better knowledge, these decisions could more accurately reflect the opportunity costs of pursuing non-economic objectives.

Biological role of AKT, and regulation of AKT signaling pathway by thymoquinone: perspectives in cancer therapeutics

2020 ◽  
Vol 20 ◽  
Author(s):  
Md. Junaid ◽  
Yeasmin Akter ◽  
Syeda Samira Afrose ◽  
Mousumi Tania ◽  
Md. Asaduzzaman Khan
Keyword(s):  
Clinical Trials ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Inhibitory Effect ◽  
Akt Signaling ◽  
Review Article ◽  
Therapeutic Drug ◽  
Akt Signaling Pathway ◽  
Anti Cancer

Background: AKT/PKB is an important enzyme with numerous biological functions, and its overexpression is related to the carcinogenesis. AKT stimulates different signaling pathways that are downstream of activated tyrosine kinases and phosphatidylinositol 3-kinase, hence functions as an important target for anti-cancer drugs. Objective: In this review article, we have interpreted the role of AKT signaling pathways in cancer and natural inhibitory effect of Thymoquinone (TQ) in AKT and its possible mechanism. Method: We have collected the updated information and data on AKT, their role in cancer and inhibitory effect of TQ in AKT signaling pathway from google scholar, PubMed, Web of Science, Elsevier, Scopus and many more. Results: There are many drugs already developed, which can target AKT, but very few among them have passed clinical trials. TQ is a natural compound, mainly found in black cumin, which has been found to have potential anti-cancer activities. TQ targets numerous signaling pathways, including AKT, in different cancers. In fact, many studies revealed that AKT is one of the major targets of TQ. The preclinical success of TQ suggests its clinical studies on cancer. Conclusion: This review article summarizes the role of AKT in carcinogenesis, its potent inhibitors in clinical trials, and how TQ acts as an inhibitor of AKT and TQ’s future as a cancer therapeutic drug.

The Role of Cytokines in Interactions of Mesenchymal Stem Cells and Breast Cancer Cells

2020 ◽  
Vol 15 ◽  
Author(s):  
Hariharan Jayaraman ◽  
Nalinkanth V. Ghone ◽  
Ranjith Kumaran R ◽  
Himanshu Dashora
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cell Communication ◽  
Extra Cellular Matrix ◽  
Cytokine Signaling ◽  
Cellular Matrix

: Mesenchymal stem cells because of its high proliferation, differentiation, regenerative capacity, and ease of availability have been a popular choice in cytotherapy. Mesenchymal Stem Cells (MSCs) have a natural tendency to home in a tumor microenvironment and acts against it, owing to the similarity of the latter to an injured tissue environment. Several studies have confirmed the recruitment of MSCs by tumor through various cytokine signaling that brings about phenotypic changes to cancer cells, thereby promoting migration, invasion, and adhesion of cancer cells. The contrasting results on MSCs as a tool for cancer cytotherapy may be due to the complex cell to cell interaction in the tumor microenvironment, which involves various cell types such as cancer cells, immune cells, endothelial cells, and cancer stem cells. Cell to cell communication can be simple or complex and it is transmitted through various cytokines among multiple cell phenotypes, mechano-elasticity of the extra-cellular matrix surrounding the cancer cells, and hypoxic environments. In this article, the role of the extra-cellular matrix proteins and soluble mediators that acts as communicators between mesenchymal stem cells and cancer cells has been reviewed specifically for breast cancer, as it is the leading member of cancer malignancies. The comprehensive information may be beneficial in finding a new combinatorial cytotherapeutic strategy using MSCs by exploiting the cross-talk between mesenchymal stem cells and cancer cells for treating breast cancer.

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