Endothelial cell (EC) recruitment is central to the vascularization of tumors. Although several proteoglycans have been implicated in cancer and angiogenesis, their roles in EC recruitment and vascularization during tumorigenesis remain poorly understood. Here, we reveal that Agrin, which is secreted in liver cancer, promotes angiogenesis by recruiting ECs within tumors and metastatic lesions and facilitates adhesion of cancer cells to ECs. In ECs, Agrin-induced angiogenesis and adherence to cancer cells are mediated by Integrin-β1, Lrp4-MuSK pathways involving focal adhesion kinase. Mechanistically, we uncover that Agrin regulates VEGFR2 levels that sustain the angiogenic property of ECs and adherence to cancer cells. Agrin attributes an ECM stiffness-based stabilization of VEGFR2 by enhancing interactions with Integrin-β1-Lrp4 and additionally stimulates endothelial nitric-oxide synthase (e-NOS) signaling. Therefore, we propose that cross-talk between Agrin-expressing cancer and ECs favor angiogenesis by sustaining the VEGFR2 pathway.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.celrep.2019.06.036 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Preparation of capecitabine-poly(p-dioxanone) electrospraying nanoparticles and influence of particle size on their colorectal cancer inhibitive efficiency.
J Biomater Appl
March 2025
Department of Chemistry, School of Pharmacy, North Sichuan Medical College, Nanchong, China.
Colorectal cancer is the fourth leading cause of cancer-related deaths worldwide. Capecitabine is a chemotherapeutic agent commonly used for the treatment of colon cancer. To realize local sustained release, promote efficient local intracellular transport, and mitigate the systemic toxic effects of capecitabine, a capecitabine prodrug, capecitabine-poly (p-dioxanone) (Cap-PPDO), was successfully synthesized.
View Article and Find Full Text PDFIL-15 complex enhances agonistic anti-CD40 + anti-PDL1 by correcting the T-bet to Tox ratio in CD8+ T cells infiltrating pancreatic ductal adenocarcinoma.
Cancer Immunol Res
March 2025
University of Minnesota, Minneapolis, MN, United States.
Agonistic anti-CD40 with anti-PD-1 can elicit objective responses in a small number of patients with pancreatic ductal adenocarcinoma (PDA). Better understanding of their individual effects on the PDA tumor microenvironment will help inform new strategies to further improve outcomes. Herein, we map tumor-specific CD8+ T-cell differentiation following agonistic anti-CD40 and/or anti-PDL1 in PDA.
View Article and Find Full Text PDFA novel dominant-negative variant of IRF8 in a mother and son: Clinical, phenotypic and biological characteristics.
J Allergy Clin Immunol
March 2025
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minn. Electronic address:
Background: The few reported patients with pathogenic IRF8 variants have manifested 2 distinct phenotypes: (1) an autosomal recessive severe immunodeficiency with significant neutrophilia and absence of or significant decrease in monocytes and dendritic cells and (2) a dominant-negative form with only a decrease in conventional type 2 dendritic cells (cDC2s) and susceptibility to mycobacterial disease.
Objectives: Genetic testing of a child with persistent EBV viremia identified a novel IRF8 variant: c.1279dupT (p.
Nanozyme-Based Strategies in Cancer Immunotherapy: Overcoming Resistance to Enhance Therapeutic Efficacy.
Aging Dis
February 2025
Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Nanozymes, which are nanomaterials that replicate the catalytic activities of natural enzymes in biological systems, have recently demonstrated considerable potential in improving cancer immunotherapy by altering the tumor microenvironment. Nanozyme-driven immune responses represent an innovative therapeutic modality with high effectiveness and minimal side effects. These nanozymes activate the immune system to specifically recognize and destroy cancer cells.
View Article and Find Full Text PDFKLF family members control expression of genes required for tissue macrophage identities.
J Exp Med
May 2025
Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Tissue-resident macrophages adopt distinct gene expression profiles and exhibit functional specialization based on their tissue of residence. Recent studies have begun to define the signals and transcription factors that induce these identities. Here we describe an unexpected and specific role for the broadly expressed transcription factor Krüppel-like factor 2 (KLF2) in the development of embryonically derived large cavity macrophages (LCMs) in the serous cavities.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!