Obesity-Activated Adipose-Derived Stromal Cells Promote Breast Cancer Growth and Invasion
| Autor: | Lisa M. Arendt, Gretchen Paderta, Lauren E. Hillers, Tamara Chamberlin, Joseph V. D'Amato |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research BMI body mass index animal diseases GAPDH glyceraldehyde 3-phosphate dehydrogenase Mammary gland Adipose tissue ASC adipose-derived stromal cells Metastasis Mice 0302 clinical medicine HFD high fat diet SVF stromal vascular fraction Insulin-Like Growth Factor I GFP green fluorescent protein Mammary tumor hemic and immune systems Stromal vascular fraction lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Immunohistochemistry Phenotype medicine.anatomical_structure Adipose Tissue 030220 oncology & carcinogenesis Female CD control diet tissues Original article endocrine system Stromal cell Breast Neoplasms IGF-1 insulin-like growth factor-1 Biology Diet High-Fat lcsh:RC254-282 WL weight loss 03 medical and health sciences Cell Line Tumor medicine Animals Humans Obesity SMA alpha-smooth muscle actin Mesenchymal stem cell medicine.disease eye diseases Disease Models Animal 030104 developmental biology Cell culture Cancer research Stromal Cells Biomarkers |
| Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 20, Iss 11, Pp 1161-1174 (2018) Neoplasia (New York, N.Y.) |
| ISSN: | 1476-5586 |
| Popis: | Obese women diagnosed with breast cancer have an increased risk for metastasis, and the underlying mechanisms are not well established. Within the mammary gland, adipose-derived stromal cells (ASCs) are heterogeneous cells with the capacity to differentiate into multiple mesenchymal lineages. To study the effects of obesity on ASCs, mice were fed a control diet (CD) or high-fat diet (HFD) to induce obesity, and ASCs were isolated from the mammary glands of lean and obese mice. We observed that obesity increased ASCs proliferation, decreased differentiation potential, and upregulated expression of α-smooth muscle actin, a marker of activated fibroblasts, compared to ASCs from lean mice. To determine how ASCs from obese mice impacted tumor growth, we mixed ASCs isolated from CD- or HFD-fed mice with mammary tumor cells and injected them into the mammary glands of lean mice. Tumor cells mixed with ASCs from obese mice grew significantly larger tumors and had increased invasion into surrounding adipose tissue than tumor cells mixed with control ASCs. ASCs from obese mice demonstrated enhanced tumor cell invasion in culture, a phenotype associated with increased expression of insulin-like growth factor-1 (IGF-1) and abrogated by IGF-1 neutralizing antibodies. Weight loss induced in obese mice significantly decreased expression of IGF-1 from ASCs and reduced the ability of the ASCs to induce an invasive phenotype. Together, these results suggest that obesity enhances local invasion of breast cancer cells through increased expression of IGF-1 by mammary ASCs, and weight loss may reverse this tumor-promoting phenotype. |
| Databáze: | OpenAIRE |
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