RESUMO
BACKGROUND: 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. METHODS: 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 < 25). RESULTS: We found that obASCs promote a pro-metastatic phenotype by upregulating genes associated with epithelial-to-mesenchymal transition and promoting migration in vitro. We confirmed our findings using a TNBC patient-derived xenograft (PDX) model. PDX tumors grown in the presence of obASCS in SCID/beige mice had increased circulating HLA1+ human cells as well as increased numbers of CD44+CD24- cancer stem cells in the peripheral blood. Exposure of the TNBC PDX to obASCs also increased the formation of metastases. The knockdown of leptin expression in obASCs suppressed the pro-metastatic effects of obASCs. CONCLUSIONS: Leptin signaling is a potential mechanism through which obASCs promote metastasis of TNBC in both in vitro and in vivo analyses.
Assuntos
Tecido Adiposo/citologia , Transformação Celular Neoplásica/metabolismo , Leptina/biossíntese , Células-Tronco/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Animais , Biópsia , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica/genética , Técnicas de Cocultura , Modelos Animais de Doenças , Feminino , Perfilação da Expressão Gênica , Técnicas de Inativação de Genes , Humanos , Leptina/genética , Camundongos , Obesidade/metabolismo , Neoplasias de Mama Triplo Negativas/etiologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
This paper presents a concept using field cameras in combination with Fourier transform spectrometers. The device can produce five-dimensional (position-angle-spectra) data cubes. This can lead to accurate measurements in both spectrum and distance and allows a thorough characterization of the interferometer, as well as adds passive ranging information to hyperspectral images. Shear and tilt fringes are simultaneously observed in a fixed optical path difference interferometer, and a passive spectral ranging demonstration is done in both absorption and emission for the 500-900 nm spectral bands.