دورية أكاديمية
Obesity Induces Temporally Regulated Alterations in the Extracellular Matrix That Drive Breast Tumor Invasion and Metastasis.
| العنوان: | Obesity Induces Temporally Regulated Alterations in the Extracellular Matrix That Drive Breast Tumor Invasion and Metastasis. |
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| المؤلفون: | 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 Jr; 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. |
| المصدر: | Cancer research [Cancer Res] 2024 Sep 04; Vol. 84 (17), pp. 2761-2775. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 2984705R Publication Model: Print Cited Medium: Internet ISSN: 1538-7445 (Electronic) Linking ISSN: 00085472 NLM ISO Abbreviation: Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Baltimore, Md. : American Association for Cancer Research Original Publication: Chicago [etc.] |
| مواضيع طبية MeSH: | Obesity*/metabolism , Obesity*/pathology , Obesity*/complications , Extracellular Matrix*/metabolism , Extracellular Matrix*/pathology , Diet, High-Fat*/adverse effects , Tumor Microenvironment*, Animals ; Female ; Mice ; Humans ; Neoplasm Invasiveness ; Triple Negative Breast Neoplasms/pathology ; Triple Negative Breast Neoplasms/metabolism ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Lung Neoplasms/secondary ; Breast Neoplasms/pathology ; Breast Neoplasms/metabolism ; Cell Line, Tumor ; Liver Neoplasms/secondary ; Liver Neoplasms/metabolism ; Liver Neoplasms/pathology ; Neoplasm Metastasis ; Collagen Type IV/metabolism |
| مستخلص: | 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. (©2024 American Association for Cancer Research.) |
| معلومات مُعتمدة: | METAvivor (METAvivor Research & Support); T32DK124170 National Institutes of Health (NIH); R00 CA207866 United States CA NCI NIH HHS; R01CA255742 National Institutes of Health (NIH); DP2CA271387 National Institutes of Health (NIH); R01CA255742-S1 National Institutes of Health (NIH) |
| المشرفين على المادة: | 0 (Collagen Type IV) |
| تواريخ الأحداث: | Date Created: 20240620 Date Completed: 20240904 Latest Revision: 20240904 |
| رمز التحديث: | 20240904 |
| DOI: | 10.1158/0008-5472.CAN-23-2526 |
| PMID: | 38900938 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1538-7445 |
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| DOI: | 10.1158/0008-5472.CAN-23-2526 |