scholarly journals Association between Inflammation and Function of Cell Adhesion Molecules Influence on Gastrointestinal Cancer Development

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 67
Author(s):  
Hsiang-Wei Huang ◽  
Cheng-Chih Chang ◽  
Chia-Siu Wang ◽  
Kwang-Huei Lin
Keyword(s):  
Cell Adhesion ◽  
Tumor Microenvironment ◽  
Adhesion Molecules ◽  
Inflammatory Cytokines ◽  
Gastrointestinal Cancer ◽  
Cell Adhesion Molecules ◽  
Immune Cell ◽  
Immune Escape ◽  
Checkpoint Inhibitors ◽  
Cytotoxic T Cells

Gastrointestinal cancer is highly associated with inflammatory processes inducing the release of cytokines from cancer or immune cells, including interferons, interleukins, chemokines, colony-stimulating factors, and growth factors, which promote or suppress tumor progression. Inflammatory cytokines within the tumor microenvironment promote immune cell infiltration. Infiltrating immune, and tumor-surrounding stromal cells support tumor growth, angiogenesis, metastasis, and immunosuppression through communication with inflammatory cytokines and cell adhesion molecules. Notably, infiltrating immune and tumor cells present immunosuppressive molecules, such as programmed death-ligand 1 (PD-L1) and CD80/CD86. Suppression of cytotoxic T cells promotes tumor avoidance of immune surveillance and greater malignancy. Moreover, glycosylation and sialylation of proteins hyperexpressed on the cancer cell surface have been shown to enhance immune escape and metastasis. Cytokine treatments and immune checkpoint inhibitors are widely used in clinical practice. However, the tumor microenvironment is a rapidly changing milieu involving several factors. In this review, we have provided a summary of the interactions of inflammation and cell adhesion molecules between cancer and other cell types, to improve understanding of the tumor microenvironment.

scholarly journals Cell Adhesion Molecules and Their Roles and Regulation in the Immune and Tumor Microenvironment

2019 ◽  
Vol 10 ◽  
Author(s):  
Heidi Harjunpää ◽  
Marc Llort Asens ◽  
Carla Guenther ◽  
Susanna C. Fagerholm
Keyword(s):  
Cell Adhesion ◽  
Tumor Microenvironment ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules

scholarly journals RNAi targeting multiple cell adhesion molecules reduces immune cell recruitment and vascular inflammation after myocardial infarction

2016 ◽  
Vol 8 (342) ◽  
pp. 342ra80-342ra80 ◽  
Author(s):  
Hendrik B. Sager ◽  
Partha Dutta ◽  
James E. Dahlman ◽  
Maarten Hulsmans ◽  
Gabriel Courties ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Immune Cell ◽  
Vascular Inflammation ◽  
Cell Recruitment ◽  
Multiple Cell ◽  
Immune Cell Recruitment

scholarly journals Gab2 (Grb2-Associated Binder2) Plays a Crucial Role in Inflammatory Signaling and Endothelial Dysfunction

2021 ◽  
Author(s):  
Vijay Kondreddy ◽  
Jhansi Magisetty ◽  
Shiva Keshava ◽  
L. Vijaya Mohan Rao ◽  
Usha R. Pendurthi
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Signaling Pathways ◽  
Adhesion Molecules ◽  
Inflammatory Cytokines ◽  
Crucial Role ◽  
Cell Adhesion Molecules ◽  
Neutrophil Infiltration ◽  
Inflammatory Signaling ◽  
Necrosis Factor Alpha

Objective: In response to inflammatory insult, endothelial cells express cell adhesion molecules and TF (tissue factor), leading to increased adhesion of leukocytes to the endothelium and activation of coagulation. Enhanced coagulation could further exacerbate inflammation. Identifying key signaling molecule(s) that drive both inflammation and coagulation may help devise effective therapeutic strategies to treat inflammatory and thrombotic disorders. The aim of the current study to determine the role of Gab2 (Grb2-associated binder2), which is known to play a crucial role in the signaling evoked by growth factors and antigen receptors, in inflammatory signaling pathways and contributing to vascular dysfunction. Approach and Results: WT (wild type) and Gab2-silenced endothelial cells were treated with TNFα (tumor necrosis factor alpha), IL (interleukin)-1β, or lipopolysaccharide (LPS). Activation of key signaling proteins in the inflammatory signaling pathways and expression of cell adhesion molecules, TF, and inflammatory cytokines were analyzed. Gab2 −/ − and WT littermate mice were challenged with LPS or S pneumoniae , and parameters of inflammation and activation of coagulation were assessed. Gab2 silencing in endothelial cells markedly attenuated TNFα-induced, IL-1β–induced, and LPS-induced expression of TF, cell adhesion molecules, and inflammatory cytokines/chemokines. Gab2 silencing suppressed TNFα-induced, IL-1β–induced, and LPS-induced phosphorylation and ubiquitination of TAK1 and activation of MAPKs (mitogen-activated protein kinases) and NF-κB (nuclear factor kappa B). Immunoprecipitation studies revealed that the Src kinase Fyn phosphorylates Gab2. Gab2 −/− mice are protected from LPS or S pneumoniae –induced vascular permeability, neutrophil infiltration, thrombin generation, NET formation, cytokine production, and lung injury. Conclusions: Our studies identify, for the first time, that Gab2 integrates signaling from multiple inflammatory receptors and regulates vascular inflammation and thrombosis.

Inflammatory Cytokines and Cell Adhesion Molecules in a Rat Model of Decompression Sickness

2008 ◽  
Vol 28 (2) ◽  
pp. 55-63 ◽  
Author(s):  
Nancy J. Bigley ◽  
Heather Perymon ◽  
Gloria C. Bowman ◽  
Barbara E. Hull ◽  
Harold F. Stills ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Inflammatory Cytokines ◽  
Rat Model ◽  
Cell Adhesion Molecules ◽  
Decompression Sickness

scholarly journals An Eight-Gene Hypoxia Signature Predicts Survival in Pancreatic Cancer and Is Associated With an Immunosuppressed Tumor Microenvironment

2021 ◽  
Vol 12 ◽  
Author(s):  
Raefa Abou Khouzam ◽  
Shyama Prasad Rao ◽  
Goutham Hassan Venkatesh ◽  
Nagwa Ahmed Zeinelabdin ◽  
Stephanie Buart ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Escape ◽  
Checkpoint Inhibitors ◽  
Cytotoxic T Cells ◽  
Critical Role ◽  
Cytolytic Activity ◽  
Ductal Adenocarcinoma ◽  
Immune Reactivity ◽  
Cancer Type ◽  
Hypoxia Signature

Intratumoral hypoxia is a widely established element of the pancreatic tumor microenvironment (TME) promoting immune escape, tumor invasion, and progression, while contributing to treatment resistance and poor survival. Despite this critical role, hypoxia is underrepresented in molecular signatures of pancreatic ductal adenocarcinoma (PDA) and concurrent investigations into the hypoxia-immune status are lacking. In this work a literature-based approach was applied to derive an eight-gene hypoxia signature that was validated in fourteen cancer cell lines and in a cohort of PDA. The eight-gene hypoxia signature was significantly associated with overall survival in two distinct PDA datasets and showed independent prognostic value in multivariate analysis. Comparative analysis of tumors according to their hypoxia score (high versus low) determined that tumors with high hypoxia were significantly less enriched in cytotoxic T-cells, and cytolytic activity. In addition, they had lower expression of cytokines and tumor inflammatory markers, pointing to the signature’s ability to discern an immune “cold”, hypoxic TME. Combining the signature with an immune metric highlighted a worse survival probability in patients with high hypoxia and low immune reactivity, indicating that this approach could further refine survival estimates. Hypoxia as determined by our signature, was significantly associated with certain immune checkpoint inhibitors (ICI) biomarkers, suggesting that the signature reflects an aspect of the TME that is worth pursuing in future clinical trials. This is the first work of its kind in PDA, and our findings on the hypoxia-immune tumor contexture are not only relevant for ICI but could also guide combinatorial hypoxia-mediated therapeutic strategies in this cancer type.

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