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Abstract 2398: Tumor cell-adipocyte gap junctions activate lipolysis in breast cancer

During mammary tumorigenesis, a cell-cell interface exists between adipocytes and cancer cells. Several studies have demonstrated that breast tumor cells can secrete cytokines that induce lipolysis in adjacent adipocytes. However, evidence of tumor-adjacent lipolysis in clinical samples has been lac...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2018-07, Vol.78 (13_Supplement), p.2398-2398
Main Authors: Camarda, Roman, Williams, Jeremy, Malkov, Serghei, Zimmerman, Lisa J., Manning, Suzanne, Aran, Dvir, Beardsley, Andrew, Mark, Daniel Van de, Haren, Jeffrey van, Chen, Yong, Berdan, Charles, Louie, Sharon, Mahieu, Celine, Winkler, Juliane, Willey, Elizabeth, Gagnon, John D., Shinoda, Kosaku, Ansel, K. Mark, Werb, Zena, Nomura, Daniel C., Kajimura, Shingo, Wittmann, Torsten, Butte, Atul J., Sanders, Melinda E., Liebler, Daniel C., Krings, Gregor, Shepherd, John A., Goga, Andrei
Format: Article
Language:English
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Summary:During mammary tumorigenesis, a cell-cell interface exists between adipocytes and cancer cells. Several studies have demonstrated that breast tumor cells can secrete cytokines that induce lipolysis in adjacent adipocytes. However, evidence of tumor-adjacent lipolysis in clinical samples has been lacking. We therefore assayed for lipolysis in normal tissue adjacent to breast tumors (NAT) using (1) the three-component breast composition measure, a radiographic imaging method derived from dual-energy mammography that allows lipid content of a tissue to be quantified, on breast tumors and NAT from 46 patients, (2) a publically available dataset of gene expression in primary breast tumors and NAT from 9 patients, (3) laser capture microdissection and proteomics on primary breast tumors, stroma and NAT from 75 patients, and (4) immunoblot analysis of NAT from several patient-derived and transgenic mouse models of breast cancer. We found strong evidence in all cases that lipolysis is activated in breast cancer-adjacent adipose tissue. We next set out to model the breast cancer-adipocyte interface and determine the contribution of cell-cell contact to induced lipolysis. Gap junctions are cell-cell junctions formed by proteins called connexins, which are known to transport a variety of small molecules (
ISSN:0008-5472
1538-7445
DOI:10.1158/1538-7445.AM2018-2398