In vivo microscopy reveals macrophage polarization locally promotes coherent microtubule dynamics in migrating cancer cells

Gaurav Luthria, Ran Li, Stephanie Wang, Mark Prytyskach, Rainer H. Kohler, Douglas A. Lauffenburger, Timothy J. Mitchison, Ralph Weissleder () and Miles A. Miller ()
Additional contact information
Gaurav Luthria: Massachusetts General Hospital Research Institute
Ran Li: Massachusetts General Hospital Research Institute
Stephanie Wang: Massachusetts Institute of Technology
Mark Prytyskach: Massachusetts General Hospital Research Institute
Rainer H. Kohler: Massachusetts General Hospital Research Institute
Douglas A. Lauffenburger: Massachusetts Institute of Technology
Timothy J. Mitchison: Harvard Medical School
Ralph Weissleder: Massachusetts General Hospital Research Institute
Miles A. Miller: Massachusetts General Hospital Research Institute

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: Abstract 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.

Date: 2020
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-17147-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17147-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-17147-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().