Journal
JOURNAL OF CELL SCIENCE
Volume 132, Issue 17, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.231563
Keywords
Angiopellosis; Circulating tumor cell cluster; Tumor cell extravasation; Cancer exodus hypothesis; Metastasis
Categories
Funding
- National Institutes of Health [HL123920, HL137093]
- National Cancer Institute [F31 CA217153]
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Metastasis accounts for the majority of all cancer deaths, yet the process remains poorly understood. A pivotal step in the metastasis process is the exiting of tumor cells from the circulation, a process known as extravasation. However, it is unclear how tumor cells extravasate and whether multicellular clusters of tumor cells possess the ability to exit as a whole or must first disassociate. In this study, we use in vivo zebrafish and mouse models to elucidate the mechanism tumor cells use to extravasate. We found that circulating tumor cells exit the circulation using the recently identified extravasation mechanism, angiopellosis, and do so as both clusters and individual cells. We further show that when melanoma and cervical cancer cells utilize this extravasation method to exit as clusters, they exhibit an increased ability to form tumors at distant sites through the expression of unique genetic profiles. Collectively, we present a new model for tumor cell extravasation of both individual and multicellular circulating tumor cells. This article has an associated First Person interview with the first author of the paper.
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