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Circulating tumor cells exit circulation while maintaining multicellularity augmenting metastatic potential
Author(s) -
Tyler A. Allen,
Dana Asad,
Emmanuel Amu,
Michael Taylor Hensley,
Jhon Cores,
Adam C. Vandergriff,
Junnan Tang,
PhuongUyen Dinh,
Deliang Shen,
Li Qiao,
Teng Su,
Shiqi Hu,
Hongxia Liang,
Heather R. Shive,
Erin Harrell,
Connor Campbell,
Xinxia Peng,
Jeffrey A. Yoder,
Ke Cheng
Publication year - 2019
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.231563
Subject(s) - extravasation , circulating tumor cell , biology , intravasation , multicellular organism , metastasis , cancer , tumor cells , melanoma , cancer cell , cancer research , zebrafish , cell , immunology , genetics , gene
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 if 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 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 tumor 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.

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