Metastasis is the leading cause of cancer fatality. A better understanding of the features that contribute to cancer metastasis is critical to the development of more effective cancer therapeutics. However, the available cancer cell models that mimic various aspects of metastasis are rather limited. Even though a large number of human cancer cell lines have been derived and collected through projects, such as the Cancer Cell Line Encyclopedia (CCLE), the metastatic abilities and patterns of these cell lines have been mainly unexplored. This is due to the large sample size of mice that are required if cell lines are to be tested individually. Here we present a systematic approach that allows for the investigation of the metastatic potentials of multiple cancer cell lines in vivo in parallel. We employed DNA barcoding to label each cancer cell line individually, and investigated the metastatic behaviors of multiple cancer cell lines in a pooled fashion, by reading out the DNA barcodes. Unique barcodes were introduced into the cancer cell lines via lentiviral transduction, and the labeled lines were pooled and inoculated into mice together for in vivo investigation. Deep-sequencing of the DNA barcode abundance in different metastasis lesions that were retrieved from different organs measured the metastatic abilities of different cell lines. As a proof of principle, we applied this method to investigate the metastatic potentials of a collection of breast cancer cell lines in vivo. Collectively, this study shows a novel methodology that can be used for investigating metastatic potential of human cancer cell lines in high throughput.
PROJECT: Parallel investigation of the cancer cell metastatic potentials via cell barcoding
The Broad is unique it its commitment to leading scientific research by asking big-picture questions. During my time here I was able to do research that is impactful and cutting-edge. The mentors and faculty I met and worked with were encouraging and invested in seeing me succeed. SRPG in particular allowed me to meet students from all walks of life and different fields, and truly embodies the idea of interdependent science.