Understanding the direct, tumor cell-intrinsic effects of PI 3-kinase (PI3K) has been a key focus of research to date. Here, we report that cancer cell-extrinsic PI3K activity, mediated by the p110α isoform of PI3K, contributes in an unexpected way to tumor angiogenesis. In syngeneic mouse models, inactivation of stromal p110α led to increased vascular density, reduced vessel size, and altered pericyte coverage. This increased vascularity lacked functionality, correlating with enhanced tumor hypoxia and necrosis, and reduced tumor growth. The role of p110α in tumor angiogenesis is multifactorial, and includes regulation of proliferation and DLL4 expression in endothelial cells. p110α in the tumor stroma is thus a regulator of vessel formation, with p110α inactivation giving rise to nonfunctional angiogenesis, which can stunt tumor growth. This type of vascular aberration differs from vascular endothelial growth factor-centered antiangiogenesis therapies, which mainly lead to vascular pruning. Inhibition of p110α may thus offer a new antiangiogenic therapeutic opportunity in cancer.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782054 | PMC |
| http://dx.doi.org/10.1084/jem.20121571 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Type IV collagen derived non-collagenous domain α6 (IV) NC1 and its derivative fragments inhibit endothelial cell proliferation and attenuates chorioallantoic membrane angiogenesis.
Cytotechnology
April 2025
Department of Genetics, Osmania University, Hyderabad, Telangana State India.
Targeting tumor angiogenesis with safe endogenous protein inhibitors is a promising therapeutic approach despite the plethora of the first line of emerging chemotherapeutic drugs. The extracellular matrix network in the blood vessel basement membrane and growth factors released from endothelial and tumor cells promote the neovascularization which supports the tumor growth. Contrastingly, small cleaved cryptic fragments of the C-terminal non collagenous domains of the same basement membrane display antiangiogenic effect.
View Article and Find Full Text PDFA Coordination Nanosystem Enables Endogenous Ferric Ion-Initiated Multi-Catalysis for Synergistic Tumor-Specific Ferroptosis and Gene Therapy.
Small
January 2025
State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, China.
Emerging evidence demonstrates that inducing ferroptosis, a nonapoptotic programmed cell death mode, holds significant potential for tumor treatment. However, current ferroptosis strategies utilizing exogenous Fenton-type heavy metal species or introducing glutathione (GSH)/glutathione peroxidase 4 (GPX4) suppressants are hampered by latent adverse effects toward organisms, while utilizing endogenous iron may cause undesirable tumor angiogenesis through specific signaling pathways. Here, a ferric ion (Fe)-responsive and DNAzyme-delivered coordination nanosystem (ZDD) is developed to achieve a novel scheme of synergistic tumor-specific ferroptosis and gene therapy, which modulates and harnesses the endogenous iron in tumors for inducing ferroptosis while intercepting tumor angiogenesis to enhance therapeutic efficacy.
View Article and Find Full Text PDFVascular Endothelial Growth Factor (VEGF) Family and the Immune System: Activators or Inhibitors?
Biomedicines
December 2024
ContendEd Net, 00166 Rome, Italy.
The vascular endothelial growth factor (VEGF) family includes key mediators of vasculogenesis and angiogenesis. VEGFs are secreted by various cells of epithelial and mesenchymal origin and by some immune cells in response to physiological and pathological stimuli. In addition, immune cells express VEGF receptors and/or co-receptors and can respond to VEGFs in an autocrine or paracrine manner.
View Article and Find Full Text PDFSingle-cell transcriptomics reveals the heterogeneity and function of mast cells in human ccRCC.
Front Immunol
January 2025
Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Introduction: The role of mast cells (MCs) in clear cell renal carcinoma (ccRCC) is unclear, and comprehensive single-cell studies of ccRCC MCs have not yet been performed.
Methods: To investigate the heterogeneity and effects of MCs in ccRCC, we studied single-cell transcriptomes from four ccRCC patients, integrating both single-cell sequencing and bulk tissue sequencing data from online sequencing databases, followed by validation via spatial transcriptomics and multiplex immunohistochemistry (mIHC).
Results: We identified four MC signature genes (TPSB2, TPSAB1, CPA3, and HPGDS).
A novel oncolytic Vaccinia virus armed with IL-12 augments antitumor immune responses leading to durable regression in murine models of lung cancer.
Front Immunol
January 2025
Sino-British Research Centre for Molecular Oncology, National Centre for International Research in Cell and Gene Therapy, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
Oncolytic vaccinia viruses (VVs) are potent stimulators of the immune system and induce immune-mediated tumor clearance and long-term surveillance against tumor recurrence. As such they are ideal treatment modalities for solid tumors including lung cancer. Here, we investigated the use of VVL-m12, a next-generation, genetically modified, interleukin-12 (IL-12)-armed VV, as a new therapeutic strategy to treat murine models of lung cancer and as a mechanism of increasing lung cancer sensitivity to antibody against programmed cell death protein 1 (α-PD1) therapy.
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!