In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 5205-5205
Abstract:
DHA is a long-chain omega-3 polyunsaturated fatty acid that has anticancer properties, including the ability to suppress tumor angiogenesis. However, the precise mechanism of DHAs anti-angiogenic activity is not well defined. It is recognized that the intercommunication between cancer cells and their microenvironment is essential to tumor angiogenesis. Exosomes are nanometer-sized extracellular vesicles that are important mediators of intercellular communication and in recent years, the role of tumor-derived exosomes in cancer progression has been realized. However, ways to limit or alter their influence on cancer progression has not been demonstrated. At this time, very little is known about the role of breast cancer derived exosomes in contributing to breast cancer progression and whether these exosomes mediate DHAs anticancer activity. To investigate, breast cancer exosomes were collected from the conditioned media of MCF7 and MDA-MB-231 breast cancer cells engineered to express GFP-tagged CD63 after treatment with DHA. We observed an increase in exosome secretion from the DHA-treated cells. Total RNA was extracted from the DHA-treated and control MCF7-derived exosomes and analyzed by small RNA sequencing. The expression of 83 exosome microRNAs was altered by DHA ( & gt;2-fold) and several of the most abundant exosomal microRNAs (miR-23b, miR-27a/b, miR-21, and miR-320b) are known to have anti-angiogenic activity. When DHA-treated MCF7 cells were co-cultured with or the collected exosomes were directly applied to endothelial cell cultures, we observed an increase in the expression of these microRNAs in endothelial cells. Furthermore, overexpression of miR-23b and miR-320b in endothelial cells decreased the expression of their pro-angiogenic target genes (PLAU, AMOTL1, NRP1 and ETS2) and significantly inhibited tube formation by endothelial cells, an effect that could be reversed by inhibition of exosome secretion via Rab27A knockdown. These results suggest that the microRNAs transferred by exosomes mediate DHAs anti-angiogenic action. Our data demonstrates that DHA alters breast cancer exosome secretion and microRNA contents that leads to the inhibition of endothelial tube formation. These results provide insight into the future possibility of developing new cancer therapeutic strategies targeting exosome secretion and content transmission. Citation Format: Bethany N. Hannafon, Karla Carpenter, William Berry, Ralf Janknecht, William Dooley, Wei-Qun Ding. Docosahexaenoic acid (DHA) alters breast cancer exosome-mediated microRNA signaling. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5205. doi:10.1158/1538-7445.AM2015-5205
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2015-5205
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2015
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
