ArticleJournal of cellular and molecular medicine2026
Gremlin-1 Drives Tumour Vascularization by Promoting Endothelial Differentiation and Angiogenesis.
Article in Journal of cellular and molecular medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Gremlin-1 is a secreted antagonist of bone morphogenetic protein (BMP) signalling, highly expressed in various malignant tumours and is associated with poor prognosis. In addition to its established pro-angiogenic activity, its potential role in endothelial differentiation in tumour contexts remains incompletely defined. Here, we investigated whether gremlin-1 contributes to tumour vascularization by promoting both endothelial differentiation and vascular recruitment. The expression of gremlin-1 in murine embryonic stem cells (ESCs) promoted tumoroid development enriched in mesodermal and endothelial lineages in vitro, as indicated by the upregulation of lineage-specific markers and the presence of CD31-positive vascular-like networks. In vivo, gremlin-1-expressing ESCs generated larger teratomas with pronounced stromal expansion and increased vascularization, while retaining multilineage differentiation capacity. Using the chick chorioallantoic membrane (CAM) assay to discriminate donor-derived vasculogenesis from host-driven angiogenesis, we observed that gremlin-1-expressing grafts exhibited enhanced growth and vascularization. Species-specific endothelial labelling revealed the presence of both ESC-derived and host-derived endothelial cells within vascular structure. Collectively, our findings identify gremlin-1 as a regulator of tissue vascularization that integrates intrinsic endothelial differentiation with extrinsic angiogenic responses, a mechanism potentially relevant to vascular remodelling in several pathological conditions including tumour growth.
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