A distinct endothelial cell population rescues the metastatic phenotype of B16 melanoma cells after ephrinB2-EphB4 interaction depletion

  • Oral e-Poster Presentations - Booth 3: Spine 2 (Tumors), September 26, 2023, 4:10 PM - 4:50 PM Background: Spinal metastasis remains a persistent and oftentimes urgent challenge in the neurosurgical operating room. We aim to understand metastatic spread to the spinal bone on a molecular level in endothelial cells and tumor cells to facilitate improved therapeutic approaches and diagnostics. Methods: We established a murine syngeneic spinal bone metastasis model. In vivo dissemination was first evaluated using fluorescent beads, followed by murine cancer cell lines (B16, LLC1). We investigated short-term seeding and long-term growth to identify correlations between seeding and tumor formation. EphrinB2-Eph4 interaction has been described as a crucial mediator of spinal bone metastasis. Transient (pharmacological) and permanent (genetical) ephrinB2-Eph4 interventions were performed. Results: Dissemination of microbeads to distinct spinal segments depended on segment and particle size. Disseminated tumor cells on the contrary showed less frequent arrest in the bone and equal distribution among segments. EphrinB2 intervention changed the dissemination behavior towards the lumbar segment. Interestingly, only transient intervention retained this distribution, permanent ephrinB2 depletion on endothelial cells (efnb2iΔEC) resulted in equal dispersion of metastases. Histological staining revealed a reduction of Endomucin (Emcn) positive structures in combination with a reduction of Type H (Emcn high/CD31 high) endothelial cells in naïve efnb2iΔEC animals. In tumor tissue, these Type H endothelial cells were unaffected. However, an increase in CD31-expressing endothelial cells was observed under endothelial ephrinB2 depletion. These CD31-expressing endothelial cells have been recently described as Type E (Emcn low/CD31 high) and implicated in angiogenesis and osteogenesis. Conclusions: We here describe a subpopulation of endothelial cells in efnb2iΔEC mice that seems to resemble pro-angiogenic and possibly pro-adhesive type E endothelial cells. Based on these finding we propose a compensatory pro-angiogenic mechanism in efnb2iΔEC mice that is highjacking pre-existing developmental pathways, which is critical for late-stage spinal metastatic growth independent of the initial seeding and extravasation of metastatic cells.

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Author:Maximilian GeisslerORCiD, András PiffkóORCiDGND, Peter VajkoczyORCiDGND, Marcus Alexander CzabankaORCiDGND, Thomas BrogginiORCiDGND
Parent Title (English):Brain and Spine
Place of publication:Amsterdam
Document Type:Conference Proceeding
Date of Publication (online):2023/09/26
Date of first Publication:2023/09/26
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Contributing Corporation:European Association of Neurosurgical Societies Congress (2023 : Barcelona)
Release Date:2023/10/30
Issue:Supplement 1, 102098
Article Number:102098
Page Number:1
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International