Vascular mimicry as a facilitator of melanoma brain metastasis.

Autor: Provance OK; Department of Medicine, Section of Medical Oncology, Yale University School of Medicine, 333 Cedar Street, SHM234E, New Haven, CT, 06520, USA., Oria VO; Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark., Tran TT; Department of Medicine, Section of Medical Oncology, Yale University School of Medicine, 333 Cedar Street, SHM234E, New Haven, CT, 06520, USA., Caulfield JI; Department of Medicine, Section of Medical Oncology, Yale University School of Medicine, 333 Cedar Street, SHM234E, New Haven, CT, 06520, USA., Zito CR; Department of Medicine, Section of Medical Oncology, Yale University School of Medicine, 333 Cedar Street, SHM234E, New Haven, CT, 06520, USA.; Department of Biology, School of Arts, Sciences, Business, and Education, University of Saint Joseph, West Hartford, CT, USA., Aguirre-Ducler A; Department of Pathology, Yale University School of Medicine, New Haven, CT, USA., Schalper KA; Department of Pathology, Yale University School of Medicine, New Haven, CT, USA., Kluger HM; Department of Medicine, Section of Medical Oncology, Yale University School of Medicine, 333 Cedar Street, SHM234E, New Haven, CT, 06520, USA., Jilaveanu LB; Department of Medicine, Section of Medical Oncology, Yale University School of Medicine, 333 Cedar Street, SHM234E, New Haven, CT, 06520, USA. lucia.jilaveanu@yale.edu.
Jazyk: angličtina
Zdroj: Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2024 Apr 18; Vol. 81 (1), pp. 188. Date of Electronic Publication: 2024 Apr 18.
DOI: 10.1007/s00018-024-05217-z
Abstrakt: Melanoma has the highest propensity among solid tumors to metastasize to the brain. Melanoma brain metastases (MBM) are a leading cause of death in melanoma and affect 40-60% of patients with late-stage disease. Therefore, uncovering the molecular mechanisms behind MBM is necessary to enhance therapeutic interventions. Vascular mimicry (VM) is a form of neovascularization linked to invasion, increased risk of metastasis, and poor prognosis in many tumor types, but its significance in MBM remains poorly understood. We found that VM density is elevated in MBM compared to paired extracranial specimens and is associated with tumor volume and CNS edema. In addition, our studies indicate a relevant role of YAP and TAZ, two transcriptional co-factors scarcely studied in melanoma, in tumor cell-vasculogenesis and in brain metastasis. We recently demonstrated activation of the Hippo tumor suppressor pathway and increased degradation of its downstream targets YAP and TAZ in a metastasis impaired cell line model. In the current study we establish the utility of anti-YAP/TAZ therapy in mouse models of metastatic melanoma whereby treatment effectively inhibits VM and prolongs survival of mice with MBM. The data presented herein suggest that VM may be an important and targetable mechanism in melanoma and that VM inhibition might be useful for treating MBM, an area of high unmet clinical need, thus having important implications for future treatment regimens for these patients.
(© 2024. The Author(s).)
Databáze: MEDLINE
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