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Obesity Induces Temporally Regulated Alterations in the Extracellular Matrix That Drive Breast Tumor Invasion and Metastasis.
Conner, Sydney J; Borges, Hannah B; Guarin, Justinne R; Gerton, Thomas J; Yui, Anna; Salhany, Kenneth J; Mensah, Diamond N; Hamilton, Grace A; Le, Giang H; Lew, Katherine C; Zhang, Crystal; Oudin, Madeleine J.
Afiliación
  • Conner SJ; Department of Biomedical Engineering, Tufts University, Medford, Massachusetts.
  • Borges HB; Department of Biomedical Engineering, Tufts University, Medford, Massachusetts.
  • Guarin JR; Department of Biomedical Engineering, Tufts University, Medford, Massachusetts.
  • Gerton TJ; Department of Biomedical Engineering, Tufts University, Medford, Massachusetts.
  • Yui A; Department of Biomedical Engineering, Tufts University, Medford, Massachusetts.
  • Salhany KJ; Department of Biomedical Engineering, Tufts University, Medford, Massachusetts.
  • Mensah DN; Department of Biomedical Engineering, Tufts University, Medford, Massachusetts.
  • Hamilton GA; Department of Biomedical Engineering, Tufts University, Medford, Massachusetts.
  • Le GH; Department of Biomedical Engineering, Tufts University, Medford, Massachusetts.
  • Lew KC; Department of Biomedical Engineering, Tufts University, Medford, Massachusetts.
  • Zhang C; Department of Biomedical Engineering, Tufts University, Medford, Massachusetts.
  • Oudin MJ; Department of Biomedical Engineering, Tufts University, Medford, Massachusetts.
Cancer Res ; 84(17): 2761-2775, 2024 Sep 04.
Article en En | MEDLINE | ID: mdl-38900938
ABSTRACT
Obesity is associated with increased incidence and metastasis of triple-negative breast cancer, an aggressive breast cancer subtype. The extracellular matrix (ECM) is a major component of the tumor microenvironment that drives metastasis. To characterize the temporal effects of age and high-fat diet (HFD)-driven weight gain on the ECM, we injected allograft tumor cells at 4-week intervals into mammary fat pads of mice fed a control or HFD, assessing tumor growth and metastasis and evaluating the ECM composition of the mammary fat pads, lungs, and livers. Tumor growth was increased in obese mice after 12 weeks on HFD. Liver metastasis increased in obese mice only at 4 weeks, and elevated body weight correlated with increased metastasis to the lungs but not the liver. Whole decellularized ECM coupled with proteomics indicated that early stages of obesity were sufficient to induce changes in the ECM composition. Obesity led to an increased abundance of the proinvasive ECM proteins collagen IV and collagen VI in the mammary glands and enhanced the invasive capacity of cancer cells. Cells of stromal vascular fraction and adipose stem and progenitor cells were primarily responsible for secreting collagen IV and collagen VI, not adipocytes. Longer exposure to HFD increased the invasive potential of ECM isolated from the lungs and liver, with significant changes in ECM composition found in the liver with short-term HFD exposure. Together, these data suggest that changes in the breast, lungs, and liver ECM underlie some of the effects of obesity on triple-negative breast cancer incidence and metastasis.

Significance:

Organ-specific extracellular matrix changes in the primary tumor and metastatic microenvironment are mechanisms by which obesity contributes to breast cancer progression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Matriz Extracelular / Microambiente Tumoral / Dieta Alta en Grasa / Obesidad Límite: Animals / Female / Humans Idioma: En Revista: Cancer Res Año: 2024 Tipo del documento: Article 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: Matriz Extracelular / Microambiente Tumoral / Dieta Alta en Grasa / Obesidad Límite: Animals / Female / Humans Idioma: En Revista: Cancer Res Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos