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The murine metastatic microenvironment of experimental brain metastases of breast cancer differs by host age in vivo: a proteomic study.
Hunt, Allison L; Khan, Imran; Wu, Alex M L; Makohon-Moore, Sasha C; Hood, Brian L; Conrads, Kelly A; Abulez, Tamara; Ogata, Jonathan; Mitchell, Dave; Gist, Glenn; Oliver, Julie; Wei, Debbie; Chung, Monika A; Rahman, Samiur; Bateman, Nicholas W; Zhang, Wei; Conrads, Thomas P; Steeg, Patricia S.
Afiliação
  • Hunt AL; Women's Health Integrated Research Center, Inova Women's Service Line, Inova Health System, 3289 Woodburn Rd, Annandale, VA, 22042, USA.
  • Khan I; Gynecologic Cancer Center of Excellence and the Women's Health Integrated Research Center, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD, 20889, USA.
  • Wu AML; Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Building 37, Room 1126, Bethesda, MD, 20892, USA.
  • Makohon-Moore SC; Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Building 37, Room 1126, Bethesda, MD, 20892, USA.
  • Hood BL; Zymeworks Inc, Vancouver, BC, V5T 1G4, Canada.
  • Conrads KA; Gynecologic Cancer Center of Excellence and the Women's Health Integrated Research Center, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD, 20889, USA.
  • Abulez T; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, 6720A Rockledge Drive, Suite 100, Bethesda, MD, 20817, USA.
  • Ogata J; Gynecologic Cancer Center of Excellence and the Women's Health Integrated Research Center, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD, 20889, USA.
  • Mitchell D; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, 6720A Rockledge Drive, Suite 100, Bethesda, MD, 20817, USA.
  • Gist G; Gynecologic Cancer Center of Excellence and the Women's Health Integrated Research Center, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD, 20889, USA.
  • Oliver J; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, 6720A Rockledge Drive, Suite 100, Bethesda, MD, 20817, USA.
  • Wei D; Gynecologic Cancer Center of Excellence and the Women's Health Integrated Research Center, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD, 20889, USA.
  • Chung MA; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, 6720A Rockledge Drive, Suite 100, Bethesda, MD, 20817, USA.
  • Rahman S; Gynecologic Cancer Center of Excellence and the Women's Health Integrated Research Center, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD, 20889, USA.
  • Bateman NW; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, 6720A Rockledge Drive, Suite 100, Bethesda, MD, 20817, USA.
  • Zhang W; Gynecologic Cancer Center of Excellence and the Women's Health Integrated Research Center, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD, 20889, USA.
  • Conrads TP; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, 6720A Rockledge Drive, Suite 100, Bethesda, MD, 20817, USA.
  • Steeg PS; Gynecologic Cancer Center of Excellence and the Women's Health Integrated Research Center, Department of Gynecologic Surgery and Obstetrics, Uniformed Services University and Walter Reed National Military Medical Center, 8901 Wisconsin Avenue, Bethesda, MD, 20889, USA.
Clin Exp Metastasis ; 2023 Nov 02.
Article em En | MEDLINE | ID: mdl-37917186
ABSTRACT
Breast cancer in young patients is known to exhibit more aggressive biological behavior and is associated with a less favorable prognosis than the same disease in older patients, owing in part to an increased incidence of brain metastases. The mechanistic explanations behind these findings remain poorly understood. We recently reported that young mice, in comparison to older mice, developed significantly greater brain metastases in four mouse models of triple-negative and luminal B breast cancer. Here we have performed a quantitative mass spectrometry-based proteomic analysis to identify proteins potentially contributing to age-related disparities in the development of breast cancer brain metastases. Using a mouse hematogenous model of brain-tropic triple-negative breast cancer (MDA-MB-231BR), we harvested subpopulations of tumor metastases, the tumor-adjacent metastatic microenvironment, and uninvolved brain tissues via laser microdissection followed by quantitative proteomic analysis using high resolution mass spectrometry to characterize differentially abundant proteins potentially contributing to age-dependent rates of brain metastasis. Pathway analysis revealed significant alterations in signaling pathways, particularly in the metastatic microenvironment, modulating tumorigenesis, metabolic processes, inflammation, and neuronal signaling. Tenascin C (TNC) was significantly elevated in all laser microdissection (LMD) enriched compartments harvested from young mice relative to older hosts, which was validated and confirmed by immunoblot analysis of whole brain lysates. Additional in vitro studies including migration and wound-healing assays demonstrated TNC as a positive regulator of tumor cell migration. These results provide important new insights regarding microenvironmental factors, including TNC, as mechanisms contributing to the increased brain cancer metastatic phenotype observed in young breast cancer patients.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article