The Role of Extracellular Vesicles in Metastasis
Technical Report,01 Oct 2017,30 Sep 2018
LAWRENCE LIVERMORE NATIONAL LAB CA LIVERMORE United States
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The proposed work addresses the dire need for new platforms for ESV isolation and precise, quantitative characterization of each cancerous ESV subpopulations role in cargo transfer. Specifically, we aim to 1 optimize an existing microfluidic separation platform to efficiently isolate ESV subpopulations from the cells and from each other originating from breast cancer cell lines with a range of metastatic character, 2 engineer breast cancer cell lines with fluorescent and radio labeled ESV sub-populations for individual tracking, and 3 use accelerator mass spectrometry AMS, which allows extremely sensitive rare-molecule detection, to quantify low levels of tumor-derived RNA transferred via ESVs to osteoblasts. These bone cells represent the most common tissue target for breast cancer metastasis, and we will mimic ESV-mediated cancer invasion and metastasis by growing the cancerous and bone cells together in a trans-well cell co-culture system. The use of these molecular and physical tools in combination specifically to address cancer invasiveness and mechanisms of metastasisis unprecedented. This study will yield the first quantitative data on which ESV subpopulations exosomes, MVs, oroncosomes manipulate the tumor microenvironment, the ESV cargo transferred, and how this differs across the range of cell metastatic potential.
- Medicine and Medical Research