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Curr Biol. 2015 Jan 19;25(2):242-250. doi: 10.1016/j.cub.2014.11.030. Epub 2015 Jan 8.

Collective cell motility promotes chemotactic prowess and resistance to chemorepulsion.

Author information

1
FIRC Institute for Molecular Oncology (IFOM), Milan 20139, Italy.
2
Institute of Molecular and Cell Biology (IMCB), A(∗)STAR, Singapore 138673, Singapore.
3
INSERM, UMR1043, Toulouse 31024, France; CNRS, UMR5282, Toulouse 31024, France; Université Toulouse III Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse 31024, France.
4
Department of Chemical Physics, The Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: nir.gov@weizmann.ac.il.
5
FIRC Institute for Molecular Oncology (IFOM), Milan 20139, Italy; Dipartimento di Science della Salute, San Paolo, Università degli Studi di Milano, Milan 20142, Italy. Electronic address: giorgio.scita@ifom.eu.
6
INSERM, UMR1043, Toulouse 31024, France; CNRS, UMR5282, Toulouse 31024, France; Université Toulouse III Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse 31024, France. Electronic address: loic.dupre@inserm.fr.

Abstract

Collective cell migration is a widespread biological phenomenon, whereby groups of highly coordinated, adherent cells move in a polarized fashion. This migration mode is a hallmark of tissue morphogenesis during development and repair and of solid tumor dissemination. In addition to circulating as solitary cells, lymphoid malignancies can assemble into tissues as multicellular aggregates. Whether malignant lymphocytes are capable of coordinating their motility in the context of chemokine gradients is, however, unknown. Here, we show that, upon exposure to CCL19 or CXCL12 gradients, malignant B and T lymphocytes assemble into clusters that migrate directionally and display a wider chemotactic sensitivity than individual cells. Physical modeling recapitulates cluster motility statistics and shows that intracluster cell cohesion results in noise reduction and enhanced directionality. Quantitative image analysis reveals that cluster migration runs are periodically interrupted by transitory rotation and random phases that favor leader cell turnover. Additionally, internalization of CCR7 in leader cells is accompanied by protrusion retraction, loss of polarity, and the ensuing replacement by new leader cells. These mechanisms ensure sustained forward migration and resistance to chemorepulsion, a behavior of individual cells exposed to steep CCL19 gradients that depends on CCR7 endocytosis. Thus, coordinated cluster dynamics confer distinct chemotactic properties, highlighting unexpected features of lymphoid cell migration.

PMID:
25578904
DOI:
10.1016/j.cub.2014.11.030
[Indexed for MEDLINE]
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