Your browser doesn't support javascript.
loading
Age-dependent loss of HAPLN1 erodes vascular integrity via indirect upregulation of endothelial ICAM1 in melanoma.
Marino-Bravante, Gloria E; Carey, Alexis E; Hüser, Laura; Dixit, Agrani; Wang, Vania; Kaur, Amanpreet; Liu, Ying; Ding, Supeng; Schnellmann, Rahel; Gerecht, Sharon; Gu, Luo; Eisinger-Mathason, T S Karin; Chhabra, Yash; Weeraratna, Ashani T.
Afiliación
  • Marino-Bravante GE; Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Carey AE; Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Hüser L; Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Dixit A; Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Wang V; Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Kaur A; Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Liu Y; Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Ding S; Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Schnellmann R; Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Gerecht S; Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Gu L; Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA.
  • Eisinger-Mathason TSK; Abramson Family Cancer Research Institute, Department of Pathology & Laboratory Medicine, Penn Sarcoma Program, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • Chhabra Y; Department of Materials Science and Engineering, Johns Hopkins Whiting School of Engineering, Baltimore, MD, USA.
  • Weeraratna AT; Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, USA.
Nat Aging ; 4(3): 350-363, 2024 Mar.
Article en En | MEDLINE | ID: mdl-38472454
ABSTRACT
Melanoma, the most lethal form of skin cancer, often has worse outcomes in older patients. We previously demonstrated that an age-related decrease in the secreted extracellular matrix (ECM) protein HAPLN1 has a role in slowing melanoma progression. Here we show that HAPLN1 in the dermal ECM is sufficient to maintain the integrity of melanoma-associated blood vessels, as indicated by increased collagen and VE-cadherin expression. Specifically, we show that HAPLN1 in the ECM increases hyaluronic acid and decreases endothelial cell expression of ICAM1. ICAM1 phosphorylates and internalizes VE-cadherin, a critical determinant of vascular integrity, resulting in permeable blood vessels. We found that blocking ICAM1 reduces tumor size and metastasis in older mice. These results suggest that HAPLN1 alters endothelial ICAM1expression in an indirect, matrix-dependent manner. Targeting ICAM1 could be a potential treatment strategy for older patients with melanoma, emphasizing the role of aging in tumorigenesis.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Cutáneas / Melanoma Límite: Aged / Animals / Humans Idioma: En Revista: Nat Aging Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Cutáneas / Melanoma Límite: Aged / Animals / Humans Idioma: En Revista: Nat Aging Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos