RT Journal Article
T1 Interactions between Adipocytes and Breast Cancer Cells Stimulate Cytokine Production and Drive Src/Sox2/miR-302b-Mediated Malignant Progression.
A1 Picon-Ruiz, Manuel
A1 Pan, Chendong
A1 Drews-Elger, Katherine
A1 Jang, Kibeom
A1 Besser, Alexandra H
A1 Zhao, Dekuang
A1 Morata-Tarifa, Cynthia
A1 Kim, Minsoon
A1 Ince, Tan A
A1 Azzam, Diana J
A1 Wander, Seth A
A1 Wang, Bin
A1 Ergonul, Burcu
A1 Datar, Ram H
A1 Cote, Richard J
A1 Howard, Guy A
A1 El-Ashry, Dorraya
A1 Torné-Poyatos, Pablo
A1 Marchal, Juan A
A1 Slingerland, Joyce M
K1 Breast Neoplasms
K1 Disease Progression
K1 Mice
K1 RNA, Messenger
K1 Signal Transduction
AB Consequences of the obesity epidemic on cancer morbidity and mortality are not fully appreciated. Obesity is a risk factor for many cancers, but the mechanisms by which it contributes to cancer development and patient outcome have yet to be fully elucidated. Here, we examined the effects of coculturing human-derived adipocytes with established and primary breast cancer cells on tumorigenic potential. We found that the interaction between adipocytes and cancer cells increased the secretion of proinflammatory cytokines. Prolonged culture of cancer cells with adipocytes or cytokines increased the proportion of mammosphere-forming cells and of cells expressing stem-like markers in vitro. Furthermore, contact with immature adipocytes increased the abundance of cancer cells with tumor-forming and metastatic potential in vivo. Mechanistic investigations demonstrated that cancer cells cultured with immature adipocytes or cytokines activated Src, thus promoting Sox2, c-Myc, and Nanog upregulation. Moreover, Sox2-dependent induction of miR-302b further stimulated cMYC and SOX2 expression and potentiated the cytokine-induced cancer stem cell-like properties. Finally, we found that Src inhibitors decreased cytokine production after coculture, indicating that Src is not only activated by adipocyte or cytokine exposures, but is also required to sustain cytokine induction. These data support a model in which cancer cell invasion into local fat would establish feed-forward loops to activate Src, maintain proinflammatory cytokine production, and increase tumor-initiating cell abundance and metastatic progression. Collectively, our findings reveal new insights underlying increased breast cancer mortality in obese individuals and provide a novel preclinical rationale to test the efficacy of Src inhibitors for breast cancer treatment.
PB American Association for Cancer Research
YR 2015
FD 2015-10-20
LK http://hdl.handle.net/10668/9714
UL http://hdl.handle.net/10668/9714
LA en
NO Picon-Ruiz M, Pan C, Drews-Elger K, Jang K, Besser AH, Zhao D, et al. Interactions between Adipocytes and Breast Cancer Cells Stimulate Cytokine Production and Drive Src/Sox2/miR-302b-Mediated Malignant Progression. Cancer Res. 2016 Jan 15;76(2):491-504.
DS RISalud
RD Apr 6, 2025