Abstract 4957: Role of tumor-derived exosomes in growth and metastasis of breast cancer

Abstract

Abstract Breast cancer (BC) mortality rates have decreased over last 30 years, largely due to early detection and improved treatment modalities, particularly targeted therapies. However, metastasis relentlessly drives mortality. The pervasive mortality from metastasis highlights the shortcomings of traditionally accepted hypotheses on the metastatic process. The mechanisms by which malignant tumors leave the primary tumor site, invade lymphatics, and metastasize to regional lymph nodes are complex and interrelated. Exosomes are biological nanovesicles (∼30-100 nm) of endocytic origin. Exosomes mediate local and horizontal transfer of information, such as mRNAs, miRNAs and proteins. They are indicated to play a significant role in the genesis of tumor, growth and metastasis. Recent advances in the exosome biology suggest that tumor-derived exosomes (TDEs) are critical mediators of tumorigenesis and can incite a pro-angiogenic signaling program capable of remodeling tissue matrices. However, the role of TDEs in BC metastasis remains elusive. In this study, we examined the role of exosomes in breast cancer metastasis using cell culture studies. We made the following observations: i) exosomes derived from BC cells had a mean size of 92 nm and carried exosomal marker proteins CD63 and CD81, ii) uptake of exosomes from highly metastatic BC cells (MDA-MB-231) by non-metastatic recipient cells (BT474 and T47D), iii) faster wound healing rate, increased migratory behavior, and invasiveness in recipient cells treated with metastatic BC exosomes, iv) increased endothelial cell tube formation, reflective of angiogenesis ability with exosomes from metastatic BC cells, v) modulation in expression levels of key EMT-associated proteins in non-metastatic cells treated with metastatic BC exosomes favoring EMT shift, vi) difference in metastasis-associated miRNAs levels in exosomes from invasive and non-invasive BC cells. Our data that suggest exosomes from metastatic BC cells carry the cargo essential for EMT and have the ability to change phenotypic traits of the recipient cells. Determining the role of exosomes in BC metastasis and characterization of BC exosomes components (proteins, mRNA and miRNA) will have great potential to uncover new targets and lead to new therapies for metastatic disease. Citation Format: Radha Munagala, Ramesh Gupta. Role of tumor-derived exosomes in growth and metastasis of breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4957. doi:10.1158/1538-7445.AM2014-4957