Macrophage contact induces RhoA GTPase signaling to trigger tumor cell intravasation

M. Roh-Johnson, J. J. Bravo-Cordero, A. Patsialou, Ved P. Sharma, Peng Guo, H. Liu, Louis Hodgson, John S. Condeelis

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Most cancer patients die as a result of metastasis, thus it is important to understand the molecular mechanisms of dissemination, including intra- and extravasation. Although the mechanisms of extravasation have been vastly studied in vitro and in vivo, the process of intravasation is still unclear. Furthermore, how cells in the tumor microenvironment facilitate tumor cell intravasation is still unknown. Using high-resolution imaging, we found that macrophages enhance tumor cell intravasation upon physical contact. Macrophage and tumor cell contact induce RhoA activity in tumor cells, triggering the formation of actin-rich degradative protrusions called invadopodia, enabling tumor cells to degrade and break through matrix barriers during tumor cell transendothelial migration. Interestingly, we show that macrophage-induced invadopodium formation and tumor cell intravasation also occur in patient-derived tumor cells and in vivo models, revealing a conserved mechanism of tumor cell intravasation. Our results illustrate a novel heterotypic cell contact-mediated signaling role for RhoA, as well as yield mechanistic insight into the ability of cells within the tumor microenvironment to facilitate steps of the metastatic cascade.

Original languageEnglish (US)
Pages (from-to)4203-4212
Number of pages10
JournalOncogene
Volume33
Issue number33
DOIs
StatePublished - Aug 14 2014

Fingerprint

GTP Phosphohydrolases
Macrophages
Neoplasms
Tumor Microenvironment
Transendothelial and Transepithelial Migration
Cell Movement
Actins
Neoplasm Metastasis

Keywords

  • cancer
  • heterotypic cell contact
  • invadopodia
  • macrophages
  • RhoA biosensor
  • tumor cell intravasation

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Macrophage contact induces RhoA GTPase signaling to trigger tumor cell intravasation. / Roh-Johnson, M.; Bravo-Cordero, J. J.; Patsialou, A.; Sharma, Ved P.; Guo, Peng; Liu, H.; Hodgson, Louis; Condeelis, John S.

In: Oncogene, Vol. 33, No. 33, 14.08.2014, p. 4203-4212.

Research output: Contribution to journalArticle

Roh-Johnson, M. ; Bravo-Cordero, J. J. ; Patsialou, A. ; Sharma, Ved P. ; Guo, Peng ; Liu, H. ; Hodgson, Louis ; Condeelis, John S. / Macrophage contact induces RhoA GTPase signaling to trigger tumor cell intravasation. In: Oncogene. 2014 ; Vol. 33, No. 33. pp. 4203-4212.
@article{9150c296a07842558c39088b5bd3fbd4,
title = "Macrophage contact induces RhoA GTPase signaling to trigger tumor cell intravasation",
abstract = "Most cancer patients die as a result of metastasis, thus it is important to understand the molecular mechanisms of dissemination, including intra- and extravasation. Although the mechanisms of extravasation have been vastly studied in vitro and in vivo, the process of intravasation is still unclear. Furthermore, how cells in the tumor microenvironment facilitate tumor cell intravasation is still unknown. Using high-resolution imaging, we found that macrophages enhance tumor cell intravasation upon physical contact. Macrophage and tumor cell contact induce RhoA activity in tumor cells, triggering the formation of actin-rich degradative protrusions called invadopodia, enabling tumor cells to degrade and break through matrix barriers during tumor cell transendothelial migration. Interestingly, we show that macrophage-induced invadopodium formation and tumor cell intravasation also occur in patient-derived tumor cells and in vivo models, revealing a conserved mechanism of tumor cell intravasation. Our results illustrate a novel heterotypic cell contact-mediated signaling role for RhoA, as well as yield mechanistic insight into the ability of cells within the tumor microenvironment to facilitate steps of the metastatic cascade.",
keywords = "cancer, heterotypic cell contact, invadopodia, macrophages, RhoA biosensor, tumor cell intravasation",
author = "M. Roh-Johnson and Bravo-Cordero, {J. J.} and A. Patsialou and Sharma, {Ved P.} and Peng Guo and H. Liu and Louis Hodgson and Condeelis, {John S.}",
year = "2014",
month = "8",
day = "14",
doi = "10.1038/onc.2013.377",
language = "English (US)",
volume = "33",
pages = "4203--4212",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "33",

}

TY - JOUR

T1 - Macrophage contact induces RhoA GTPase signaling to trigger tumor cell intravasation

AU - Roh-Johnson, M.

AU - Bravo-Cordero, J. J.

AU - Patsialou, A.

AU - Sharma, Ved P.

AU - Guo, Peng

AU - Liu, H.

AU - Hodgson, Louis

AU - Condeelis, John S.

PY - 2014/8/14

Y1 - 2014/8/14

N2 - Most cancer patients die as a result of metastasis, thus it is important to understand the molecular mechanisms of dissemination, including intra- and extravasation. Although the mechanisms of extravasation have been vastly studied in vitro and in vivo, the process of intravasation is still unclear. Furthermore, how cells in the tumor microenvironment facilitate tumor cell intravasation is still unknown. Using high-resolution imaging, we found that macrophages enhance tumor cell intravasation upon physical contact. Macrophage and tumor cell contact induce RhoA activity in tumor cells, triggering the formation of actin-rich degradative protrusions called invadopodia, enabling tumor cells to degrade and break through matrix barriers during tumor cell transendothelial migration. Interestingly, we show that macrophage-induced invadopodium formation and tumor cell intravasation also occur in patient-derived tumor cells and in vivo models, revealing a conserved mechanism of tumor cell intravasation. Our results illustrate a novel heterotypic cell contact-mediated signaling role for RhoA, as well as yield mechanistic insight into the ability of cells within the tumor microenvironment to facilitate steps of the metastatic cascade.

AB - Most cancer patients die as a result of metastasis, thus it is important to understand the molecular mechanisms of dissemination, including intra- and extravasation. Although the mechanisms of extravasation have been vastly studied in vitro and in vivo, the process of intravasation is still unclear. Furthermore, how cells in the tumor microenvironment facilitate tumor cell intravasation is still unknown. Using high-resolution imaging, we found that macrophages enhance tumor cell intravasation upon physical contact. Macrophage and tumor cell contact induce RhoA activity in tumor cells, triggering the formation of actin-rich degradative protrusions called invadopodia, enabling tumor cells to degrade and break through matrix barriers during tumor cell transendothelial migration. Interestingly, we show that macrophage-induced invadopodium formation and tumor cell intravasation also occur in patient-derived tumor cells and in vivo models, revealing a conserved mechanism of tumor cell intravasation. Our results illustrate a novel heterotypic cell contact-mediated signaling role for RhoA, as well as yield mechanistic insight into the ability of cells within the tumor microenvironment to facilitate steps of the metastatic cascade.

KW - cancer

KW - heterotypic cell contact

KW - invadopodia

KW - macrophages

KW - RhoA biosensor

KW - tumor cell intravasation

UR - http://www.scopus.com/inward/record.url?scp=84906277065&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84906277065&partnerID=8YFLogxK

U2 - 10.1038/onc.2013.377

DO - 10.1038/onc.2013.377

M3 - Article

VL - 33

SP - 4203

EP - 4212

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 33

ER -