Abstract 1054: Role of exosomes in tumor growth and metastasis of lung cancer

There will be an estimated 228,190 new cases, and 159,480 deaths, from lung cancer in the United States in 2013. Cancer burdens and death are largely due to metastasis in several cancer types, including lung. Much effort has been put into study how cancer cells metastasize. Emerging evidence implicates cancer cells undergo epithelial-mesenchymal transition (EMT) leading to enhanced cell migration and invasion abilities. Exosomes are endosome-derived 30-100 nm biological nanoparticles released from all types of cells but in abundance from tumor cells. Exosomes are released into the extracellular environment and have diverse biological functions. Contents of exosomes consist of proteins and genetic material (mRNA, DNA and miRNA) from the cell of origin. Exosomes are taken up by other cells and induce both genetic and epigenetic changes. Tumor-derived exosomes have been reported to facilitate tumor growth, metastasis and drug resistance. Therefore, understanding the role of tumor-derived exosomes in cellular process would probably enable better management of cancer metastasis. With an aim to prove that exosomes carry the cargo essential for EMT transition leading to cancer metastasis, we treated non-metastatic lung cancer cells with exosomes from metastatic cancers and examined if it would increase growth rate, migratory behavior, and invasiveness of the non-aggressive cancer cells. Our findings suggested: i) exosomes isolated from the lung cancer cell lines, H1299, A549 and H522 had a mean size of 94 - 162 nm; ii) the invasive and metastatic potential of these lung cancer cell lines, as observed by wound healing, migration and invasion assays, was in the following order: H1299 > A549 >> H522; iii) non-invasive H522 lung cancer cells could uptake the PKH-67 labeled exosomes from highly invasive A549 and H1299 cells as reflected by an increased fluorescent signal; iv) the H522 cells treated with A549 or H1299 exosomes exhibited faster wound healing rate, increased migratory behavior, and invasiveness, indicating that exosomes carry the cargo essential for EMT; v) the H522 cells treated with A549 exosomes showed a greater metastatic shift than H1299 treatment; vi) analysis of key EMT-associated proteins in H522 cells treated with exosomes from A549 and H1299 cells indicated changes in expression levels favoring EMT. Expression levels of epithelial markers E-Cadherin, ZO-1, ZEB1, and β-Catenin were downregulated, whereas mesenchymal markers vimentin and Snail were upregulated. Our findings provide insights of a possible role of exosomes in EMT of lung cancer cells. These findings make exosomes a promising platform for future research of EMT (Supported by Duggan Endowment, Helmsley Funds and USPHS grant R25-CA-134283). Citation Format: Radha Munagala, Cameron Campbell, Ramesh Gupta. Role of exosomes in tumor growth and metastasis of lung 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 1054. doi:10.1158/1538-7445.AM2014-1054