Randomly distributed K14 þ breast tumor cells polarize to the leading edge and guide collective migration in response to chemical and mechanical environmental cues

Priscilla Y. Hwang, Audrey Brenot, Ashley C. King, Gregory D. Longmore, Steven George

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Collective cell migration is an adaptive, coordinated interactive process involving cell–cell and cell–extracellular matrix (ECM) microenvironmental interactions. A critical aspect of collective migration is the sensing and establishment of directional movement. It has been proposed that a subgroup of cells known as leader cells localize at the front edge of a collectively migrating cluster and are responsible for directing migration. However, it is unknown how and when leader cells arrive at the front edge and what environmental cues dictate leader cell development and behavior. Here, we addressed these questions by combining a microfluidic device design that mimics multiple tumor microenvironmental cues concurrently with biologically relevant primary, heterogeneous tumor cell organoids. Prior to migration, breast tumor leader cells (K14 þ ) were present throughout a tumor organoid and migrated (polarized) to the leading edge in response to biochemical and biomechanical cues. Impairment of either CXCR4 (biochemical responsive) or the collagen receptor DDR2 (biomechanical responsive) abrogated polarization of leader cells and directed collective migration. This work demonstrates that K14 þ leader cells utilize both chemical and mechanical cues from the microenvironment to polarize to the leading edge of collectively migrating tumors.

Original languageEnglish (US)
Pages (from-to)1899-1912
Number of pages14
JournalCancer Research
Volume79
Issue number8
DOIs
StatePublished - Apr 15 2019

Fingerprint

Cues
Breast Neoplasms
Organoids
Lab-On-A-Chip Devices
Neoplasms
Collagen Receptors
Equipment Design
Cell Movement

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Randomly distributed K14 þ breast tumor cells polarize to the leading edge and guide collective migration in response to chemical and mechanical environmental cues . / Hwang, Priscilla Y.; Brenot, Audrey; King, Ashley C.; Longmore, Gregory D.; George, Steven.

In: Cancer Research, Vol. 79, No. 8, 15.04.2019, p. 1899-1912.

Research output: Contribution to journalArticle

@article{2c58e8e6669c4d59a31b3dcdf8cec0a5,
title = "Randomly distributed K14 {\th} breast tumor cells polarize to the leading edge and guide collective migration in response to chemical and mechanical environmental cues",
abstract = "Collective cell migration is an adaptive, coordinated interactive process involving cell–cell and cell–extracellular matrix (ECM) microenvironmental interactions. A critical aspect of collective migration is the sensing and establishment of directional movement. It has been proposed that a subgroup of cells known as leader cells localize at the front edge of a collectively migrating cluster and are responsible for directing migration. However, it is unknown how and when leader cells arrive at the front edge and what environmental cues dictate leader cell development and behavior. Here, we addressed these questions by combining a microfluidic device design that mimics multiple tumor microenvironmental cues concurrently with biologically relevant primary, heterogeneous tumor cell organoids. Prior to migration, breast tumor leader cells (K14 {\th} ) were present throughout a tumor organoid and migrated (polarized) to the leading edge in response to biochemical and biomechanical cues. Impairment of either CXCR4 (biochemical responsive) or the collagen receptor DDR2 (biomechanical responsive) abrogated polarization of leader cells and directed collective migration. This work demonstrates that K14 {\th} leader cells utilize both chemical and mechanical cues from the microenvironment to polarize to the leading edge of collectively migrating tumors.",
author = "Hwang, {Priscilla Y.} and Audrey Brenot and King, {Ashley C.} and Longmore, {Gregory D.} and Steven George",
year = "2019",
month = "4",
day = "15",
doi = "10.1158/0008-5472.CAN-18-2828",
language = "English (US)",
volume = "79",
pages = "1899--1912",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "8",

}

TY - JOUR

T1 - Randomly distributed K14 þ breast tumor cells polarize to the leading edge and guide collective migration in response to chemical and mechanical environmental cues

AU - Hwang, Priscilla Y.

AU - Brenot, Audrey

AU - King, Ashley C.

AU - Longmore, Gregory D.

AU - George, Steven

PY - 2019/4/15

Y1 - 2019/4/15

N2 - Collective cell migration is an adaptive, coordinated interactive process involving cell–cell and cell–extracellular matrix (ECM) microenvironmental interactions. A critical aspect of collective migration is the sensing and establishment of directional movement. It has been proposed that a subgroup of cells known as leader cells localize at the front edge of a collectively migrating cluster and are responsible for directing migration. However, it is unknown how and when leader cells arrive at the front edge and what environmental cues dictate leader cell development and behavior. Here, we addressed these questions by combining a microfluidic device design that mimics multiple tumor microenvironmental cues concurrently with biologically relevant primary, heterogeneous tumor cell organoids. Prior to migration, breast tumor leader cells (K14 þ ) were present throughout a tumor organoid and migrated (polarized) to the leading edge in response to biochemical and biomechanical cues. Impairment of either CXCR4 (biochemical responsive) or the collagen receptor DDR2 (biomechanical responsive) abrogated polarization of leader cells and directed collective migration. This work demonstrates that K14 þ leader cells utilize both chemical and mechanical cues from the microenvironment to polarize to the leading edge of collectively migrating tumors.

AB - Collective cell migration is an adaptive, coordinated interactive process involving cell–cell and cell–extracellular matrix (ECM) microenvironmental interactions. A critical aspect of collective migration is the sensing and establishment of directional movement. It has been proposed that a subgroup of cells known as leader cells localize at the front edge of a collectively migrating cluster and are responsible for directing migration. However, it is unknown how and when leader cells arrive at the front edge and what environmental cues dictate leader cell development and behavior. Here, we addressed these questions by combining a microfluidic device design that mimics multiple tumor microenvironmental cues concurrently with biologically relevant primary, heterogeneous tumor cell organoids. Prior to migration, breast tumor leader cells (K14 þ ) were present throughout a tumor organoid and migrated (polarized) to the leading edge in response to biochemical and biomechanical cues. Impairment of either CXCR4 (biochemical responsive) or the collagen receptor DDR2 (biomechanical responsive) abrogated polarization of leader cells and directed collective migration. This work demonstrates that K14 þ leader cells utilize both chemical and mechanical cues from the microenvironment to polarize to the leading edge of collectively migrating tumors.

UR - http://www.scopus.com/inward/record.url?scp=85064443190&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064443190&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-18-2828

DO - 10.1158/0008-5472.CAN-18-2828

M3 - Article

C2 - 30862718

AN - SCOPUS:85064443190

VL - 79

SP - 1899

EP - 1912

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 8

ER -