{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CD248, also known as endosialin or TEM1, is a transmembrane glycoprotein that is predominantly expressed by activated stromal fibroblasts and pericytes during development, tissue remodeling, and in pathological conditions such as cancer and fibrosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": " In the tumor microenvironment, CD248 is markedly upregulated—not on the endothelial cells themselves, but on associated perivascular mural cells and activated fibroblasts—where it modulates tumor growth, invasiveness, and metastasis. It does so by regulating pericyte migration and proliferation, mediating adhesion through binding to extracellular matrix components such as fibronectin and collagen, and by facilitating platelet‐derived growth factor (PDGF) receptor signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": " Genetic deletion or functional inhibition of CD248 has been shown to attenuate tumor progression and reduce fibrotic matrix deposition in organs such as the liver and kidney, thereby promoting a more mature vascular phenotype."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": " Moreover, CD248 is critical for capillary sprouting angiogenesis in skeletal muscle through PDGFRβ‐dependent pathways and contributes to lymph node expansion via enhanced fibroblast proliferation and migration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Hypoxic conditions further induce CD248 transcription via HIF‐2 and Ets‑1, linking its expression to microenvironmental stress responses, and its overexpression in white adipose tissue correlates with localized inflammation, fibrosis, and altered metabolic regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " Collectively, these findings position CD248 as a pivotal regulator of stromal remodeling, angiogenesis, and fibrosis in both neoplastic and non‐neoplastic settings, and they support its promise as a therapeutic target in approaches such as cancer immunotherapy and anti‐fibrotic interventions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "18"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, data from cervical carcinoma indicate that elevated expression of AEG‑1 coincides with increased levels of CD248 and other angiogenic factors (HIF‑1α, Tie2, VEGF), thereby further linking CD248 to aggressive tumor phenotypes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "John R MacFadyen, Oliver Haworth, David Roberston, et al. 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