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In vivo microscopy reveals macrophage polarization locally promotes coherent microtubule dynamics in migrating cancer cells
Name
s41467-020-17147-y.pdf
Description
Published version
Size
5.8 MB
Format
Adobe PDF
Checksum (MD5)
0f5998cbb3bcdfbd6d8e3aaa436b092e
Author(s)
Luthria, Gaurav
Li, Ran
Wang, Stephanie
Prytyskach, Mark
Kohler, Rainer H
Lauffenburger, Douglas A
Mitchison, Timothy J
Weissleder, Ralph
Miller, Miles A
Date Issued
2020
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Version
Final published version
Abstract
© 2020, The Author(s). Microtubules (MTs) mediate mitosis, directional signaling, and are therapeutic targets in cancer. Yet in vivo analysis of cancer cell MT behavior within the tumor microenvironment remains challenging. Here we developed an imaging pipeline using plus-end tip tracking and intravital microscopy to quantify MT dynamics in live xenograft tumor models. Among analyzed features, cancer cells in vivo displayed higher coherent orientation of MT dynamics along their cell major axes compared with 2D in vitro cultures, and distinct from 3D collagen gel cultures. This in vivo MT phenotype was reproduced in vitro when cells were co-cultured with IL4-polarized MΦ. MΦ depletion, MT disruption, targeted kinase inhibition, and altered MΦ polarization via IL10R blockade all reduced MT coherence and/or tumor cell elongation. We show that MT coherence is a defining feature for in vivo tumor cell dynamics and migration, modulated by local signaling from pro-tumor macrophages.
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
10.1038/S41467-020-17147-Y
