TMIC-16. INTRATUMORAL THROMBOSIS INITIATES HYPOXIA AND NECROSIS TO DRIVE TUMOR PROGRESSION THROUGH DRAMATIC TUMOR MICROENVIRONMENTAL ALTERATION
نویسندگان
چکیده
Abstract All GBM molecular subsets share the common trait of accelerated progression following necrosis which cannot be adequately explained by cellular proliferation arising from accumulated genetic alterations. We suggest that development is much more than a passive phenomenon related to rapid growth but rather driving force behind TME restructuring responsible for sustaining expansion. Current tumor models fail mimic magnitude post-necrotic within microenvironment and remain overly reliant on post-mortem analyses, obligating researchers extrapolate causal relationships between phenomena during evolution. In (WHO grade 4), most malignant primary brain tumor, vascular pathology central precede rapid, radial Mechanisms enabling selective fitness hypoxic/anoxic setting poorly understood. Nanostring GeoMX spatial profiling demonstrates M1-like TAM enrichment in non-necrotic human samples M2-like TAMs perinecrotic regions. Our immunocompetent RCAS/tv-a model aptly captures events seen gliomas, exposing dynamic temporal changes facilitate progression, incorporating unique microenvironmental stressors typically absent animal models, specifically emerging necrosis. Simultaneously, our vitro scrutinize how hypoxia-dependent signaling cells, microglia monocytes alter accumulation function TME. increase dramatically with onset necrosis, preferential localization hypoxic zone niche, supports their survival. Flow cytometry digested pre- GBMs, showed increased at 6 weeks vs. 2 (necrosis emerges week 4-5). vivo data along silico analysis Ivy GAP TCGA datasets suggests cells peri-necrotic niche attract polarize through MIF secretion, necrotic DAMP (adenosine, S100B) release, arginase secretion suppress T cells.
منابع مشابه
Tumor hypoxia does not drive differentiation of tumor - associated
Laboratory of Myeloid Cell Immunology, VIB, Brussels, Belgium Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB, Leuven, Belgium Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, K.U. Leuven, Leuven, Belgium Cell Differentiation Unit, Diabetes ...
متن کاملCancer cells exploit eIF4E2-directed synthesis of hypoxia response proteins to drive tumor progression.
Human tumors display considerable diversity in their genetic makeup but share common physiologic attributes such as a hypoxic microenvironment that contribute to the malignant phenotype. Hypoxic cells switch from eukaryotic initiation factor 4E (eIF4E) to eIF4E2 cap-dependent translation to synthesize a portion of their proteins. Here, we show that genetically distinct human cancer cells exploi...
متن کاملKinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAF
The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (Errington et al., 2014). This Regist...
متن کاملRegistered report: Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF
The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (Errington et al., 2014). This Regist...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Neuro-oncology
سال: 2022
ISSN: ['1523-5866', '1522-8517']
DOI: https://doi.org/10.1093/neuonc/noac209.1060