Leptin produced by obesity-altered adipose stem cells promotes metastasis but not tumorigenesis of triple-negative breast cancer in orthotopic xenograft and patient-derived xenograft models

• Published in: Breast cancer research : BCR 2019-05, Vol.21 (1), p.67-67, Article 67
• Main Authors: Sabol, Rachel A, Bowles, Annie C, Côté, Alex, Wise, Rachel, O'Donnell, Benjamen, Matossian, Margarite D, Hossain, Fokhrul M, Burks, Hope E, Del Valle, Luis, Miele, Lucio, Collins-Burow, Bridgette M, Burow, Matthew E, Bunnell, Bruce A
• Format: Article
• Language: English
• Subjects: Adipose stem cells; Adipose Tissue - cytology; Animals; Biopsy; Body mass index; Breast cancer; Cancer metastasis; CD44 antigen; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cells (Biology); Coculture Techniques; Complications and side effects; Disease Models, Animal; Female; Gene Expression Profiling; Gene Knockout Techniques; Genes; Health aspects; Health risk assessment; Humans; Leptin; Leptin - biosynthesis; Leptin - genetics; Medical research; Mesenchyme; Metastases; Metastasis; Mice; Mortality; Obesity; Obesity - metabolism; Patient-derived xenograft; Peripheral blood; Phenotypes; Recurrence (Disease); Risk factors; Stem cell transplantation; Stem cells; Stem Cells - metabolism; Therapeutics; Triple Negative Breast Neoplasms - etiology; Triple Negative Breast Neoplasms - metabolism; Triple Negative Breast Neoplasms - pathology; Triple-negative breast cancer; Tumorigenesis; Tumors; Womens health; Xenograft Model Antitumor Assays; Xenografts
• ISSN: 1465-542X; 1465-5411; 1465-542X
• DOI: 10.1186/s13058-019-1153-9

Breast cancer is the second leading cause of cancer deaths in the USA. Triple-negative breast cancer (TNBC) is a clinically aggressive subtype of breast cancer with high rates of metastasis, tumor recurrence, and resistance to therapeutics. Obesity, defined by a high body mass index (BMI), is an established risk factor for breast cancer. Women with a high BMI have increased incidence and mortality of breast cancer; however, the mechanisms(s) by which obesity promotes tumor progression are not well understood. In this study, obesity-altered adipose stem cells (obASCs) were used to evaluate obesity-mediated effects of TNBC. Both in vitro and in vivo analyses of TNBC cell lines were co-cultured with six pooled donors of obASCs (BMI > 30) or ASCs isolated from lean women (lnASCs) (BMI