dc.contributor.author | Heilmann, S. | |
dc.contributor.author | Ratnakumar, K. | |
dc.contributor.author | Langdon, E. M. | |
dc.contributor.author | Kansler, E. R. | |
dc.contributor.author | Kim, I. S. | |
dc.contributor.author | Campbell, N. R. | |
dc.contributor.author | Perry, E. B. | |
dc.contributor.author | Kaufman, C. K. | |
dc.contributor.author | van Rooijen, E. | |
dc.contributor.author | Lee, W. | |
dc.contributor.author | Iacobuzio-Donahue, C. A. | |
dc.contributor.author | Zon, L. I. | |
dc.contributor.author | Xavier, J. B. | |
dc.contributor.author | White, R. M. | |
dc.contributor.author | Hynes, Richard O. | |
dc.contributor.author | McMahon, Amy J. | |
dc.date.accessioned | 2017-03-06T16:47:27Z | |
dc.date.available | 2017-03-06T16:47:27Z | |
dc.date.issued | 2015-08 | |
dc.date.submitted | 2015-05 | |
dc.identifier.issn | 0008-5472 | |
dc.identifier.issn | 1538-7445 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/107192 | |
dc.description.abstract | Metastasis is the defining feature of advanced malignancy, yet remains challenging to study in laboratory environments. Here, we describe a high-throughput zebrafish system for comprehensive, in vivo assessment of metastatic biology. First, we generated several stable cell lines from melanomas of transgenic mitfa-BRAF[superscript V600E];p53[superscript −/−] fish. We then transplanted the melanoma cells into the transparent casper strain to enable highly quantitative measurement of the metastatic process at single-cell resolution. Using computational image analysis of the resulting metastases, we generated a metastasis score, μ, that can be applied to quantitative comparison of metastatic capacity between experimental conditions. Furthermore, image analysis also provided estimates of the frequency of metastasis-initiating cells (∼1/120,000 cells). Finally, we determined that the degree of pigmentation is a key feature defining cells with metastatic capability. The small size and rapid generation of progeny combined with superior imaging tools make zebrafish ideal for unbiased high-throughput investigations of cell-intrinsic or microenvironmental modifiers of metastasis. The approaches described here are readily applicable to other tumor types and thus serve to complement studies also employing murine and human cell culture systems. | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Directors New Innovator Award DP2CA186572 and K08AR055368) | en_US |
dc.description.sponsorship | Melanoma Research Alliance (Young Investigator Award) | en_US |
dc.description.sponsorship | American Association for Cancer Research/American Society of Clinical Oncology (Young Investigator Award) | en_US |
dc.description.sponsorship | Memorial Sloan-Kettering Cancer Center. Alan and Sandra Gerry Metastasis Research Initiative | en_US |
dc.description.sponsorship | Howard Hughes Medical Institute | en_US |
dc.language.iso | en_US | |
dc.publisher | American Association for Cancer Research | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1158/0008-5472.can-14-3319 | en_US |
dc.rights | Creative Commons Attribution-Noncommercial-Share Alike | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | en_US |
dc.source | PMC | en_US |
dc.title | A Quantitative System for Studying Metastasis Using Transparent Zebrafish | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Heilmann, S. et al. “A Quantitative System for Studying Metastasis Using Transparent Zebrafish.” Cancer Research 75.20 (2015): 4272–4282. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.department | Koch Institute for Integrative Cancer Research at MIT | en_US |
dc.contributor.mitauthor | Hynes, Richard O. | |
dc.contributor.mitauthor | McMahon, Amy J. | |
dc.relation.journal | Cancer Research | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Heilmann, S.; Ratnakumar, K.; Langdon, E. M.; Kansler, E. R.; Kim, I. S.; Campbell, N. R.; Perry, E. B.; McMahon, A. J.; Kaufman, C. K.; van Rooijen, E.; Lee, W.; Iacobuzio-Donahue, C. A.; Hynes, R. O.; Zon, L. I.; Xavier, J. B.; White, R. M. | en_US |
dspace.embargo.terms | N | en_US |
dc.identifier.orcid | https://orcid.org/0000-0001-7603-8396 | |
dspace.mitauthor.error | true | |
mit.license | OPEN_ACCESS_POLICY | en_US |
mit.metadata.status | Complete | |