Microtubule destabilization is a critical checkpoint of chemotaxis and transendothelial migration in melanoma cells but not in T cells

Cell Adh Migr. 2021 Dec;15(1):166-179. doi: 10.1080/19336918.2021.1934958.

Abstract

Microtubules (MTs) control cell shape and intracellular cargo transport. The role of MT turnover in the migration of slow-moving cells through endothelial barriers remains unclear. To irreversibly interfere with MT disassembly, we have used the MT-stabilizing agent zampanolide (ZMP) in Β16F10 melanoma as amodel of slow-moving cells. ZMP-treated B16 cells failed to follow chemotactic gradients across rigid confinements and could not generate stable sub-endothelial pseudopodia under endothelial monolayers. In vivo, ZMP-treated Β16 cells failed to extravasate though lung capillaries. In contrast to melanoma cells, the chemotaxis and transendothelial migration of ZMP-treated Tcells were largely conserved. This is afirst demonstration that MT disassembly is akey checkpoint in the directional migration of cancer cells but not of lymphocytes.

Keywords: Cytoskeleton; cancer; metastasis; motility; taxol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Chemotaxis / drug effects*
  • Macrolides / pharmacology*
  • Male
  • Melanoma / pathology
  • Mice
  • Mice, Inbred C57BL
  • Microtubules / drug effects
  • Microtubules / metabolism*
  • Pseudopodia / drug effects
  • T-Lymphocytes / drug effects
  • Transendothelial and Transepithelial Migration / drug effects*

Substances

  • Macrolides
  • zampanolide

Grants and funding

This work was supported by the German-Israeli Foundation for Scientific Research and Development [I-1470-412.13/2018]; Israel Science Foundation [791/17]; Minerva Foundation; Helen and Martin Kimmel Institute for Stem Cell Research; Yeda-Sela Center for Basic Research; The Meyer Henri Cancer Endowment; Moross Integrated Cancer Center.