The ubiquitin-CXCR4 axis plays an important role in acute lung infection-enhanced lung tumor metastasis

Libo Yan, Qingchun Cai, Yan Xu

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Purpose: Our goals were to test the effect of acute lung infection on tumor metastasis and to investigate the underlying mechanisms. Experimental Design: Wecombined bacteria-induced and lipopolysaccharide (LPS)-induced acute lung injury/inflammation (ALI) mouse models with mouse metastatic models to study the effect of acute inflammation on lung metastasis in mice. The mechanisms were investigated in ex vivo, in vitro, and in vivo studies. Results: Both bacteria- and LPS-induced ALI significantly enhanced lung metastasis of four tail vein- injected mouse tumor cell lines. Bacteria also enhanced lung metastasis when 4T1 cells were orthotopically injected. The bronchoalveolar lavage fluid (BALF) from LPS- or bacteria-injected mice stimulated migration of tumor cells. In vivo tracking of metastatic RM-9 cells showed that bacterial injection enhanced early dissemination of tumor cells to the lung. The majority of the BALF migratory activity could be blocked by AMD3100, a chemokine receptor 4 (CXCR4) inhibitor. All tested cell lines expressed CXCR4. The levels of extracellular ubiquitin, but not stromal cell-derived factor-1, in BALF were significantly increased by LPS. Ubiquitin was able to induce AMD3100-sensitive migration of tumor cells. Finally, the antibacterial agent amoxicillin and the CXCR4 inhibitor AMD3100 blocked the enhancement effect of bacterial infection on tumor metastasis. Conclusions: Acute lung infection dramatically increased cancer cell homing to the lung and lung metastasis. This change may be due to an alteration of the lung microenvironment and preparation of a favorable metastatic "niche." This effect was seen in multiple cancer types and thus may have broad applications for cancer patients in prevention and/or treatment of metastasis.

Original languageEnglish
Pages (from-to)4706-4716
Number of pages11
JournalClinical Cancer Research
Volume19
Issue number17
DOIs
StatePublished - Sep 1 2013

Fingerprint

Ubiquitin
Neoplasm Metastasis
Lung
Infection
Lipopolysaccharides
Neoplasms
Bronchoalveolar Lavage Fluid
Bacteria
Pneumonia
Acute Lung Injury
Cell Movement
Chemokine CXCL12
Chemokine Receptors
Amoxicillin
Tumor Cell Line
Bacterial Infections
Tail
Veins
Research Design
Anti-Bacterial Agents

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

The ubiquitin-CXCR4 axis plays an important role in acute lung infection-enhanced lung tumor metastasis. / Yan, Libo; Cai, Qingchun; Xu, Yan.

In: Clinical Cancer Research, Vol. 19, No. 17, 01.09.2013, p. 4706-4716.

Research output: Contribution to journalArticle

@article{f9205121cfa64ccd965f8352fa5c70d3,
title = "The ubiquitin-CXCR4 axis plays an important role in acute lung infection-enhanced lung tumor metastasis",
abstract = "Purpose: Our goals were to test the effect of acute lung infection on tumor metastasis and to investigate the underlying mechanisms. Experimental Design: Wecombined bacteria-induced and lipopolysaccharide (LPS)-induced acute lung injury/inflammation (ALI) mouse models with mouse metastatic models to study the effect of acute inflammation on lung metastasis in mice. The mechanisms were investigated in ex vivo, in vitro, and in vivo studies. Results: Both bacteria- and LPS-induced ALI significantly enhanced lung metastasis of four tail vein- injected mouse tumor cell lines. Bacteria also enhanced lung metastasis when 4T1 cells were orthotopically injected. The bronchoalveolar lavage fluid (BALF) from LPS- or bacteria-injected mice stimulated migration of tumor cells. In vivo tracking of metastatic RM-9 cells showed that bacterial injection enhanced early dissemination of tumor cells to the lung. The majority of the BALF migratory activity could be blocked by AMD3100, a chemokine receptor 4 (CXCR4) inhibitor. All tested cell lines expressed CXCR4. The levels of extracellular ubiquitin, but not stromal cell-derived factor-1, in BALF were significantly increased by LPS. Ubiquitin was able to induce AMD3100-sensitive migration of tumor cells. Finally, the antibacterial agent amoxicillin and the CXCR4 inhibitor AMD3100 blocked the enhancement effect of bacterial infection on tumor metastasis. Conclusions: Acute lung infection dramatically increased cancer cell homing to the lung and lung metastasis. This change may be due to an alteration of the lung microenvironment and preparation of a favorable metastatic {"}niche.{"} This effect was seen in multiple cancer types and thus may have broad applications for cancer patients in prevention and/or treatment of metastasis.",
author = "Libo Yan and Qingchun Cai and Yan Xu",
year = "2013",
month = "9",
day = "1",
doi = "10.1158/1078-0432.CCR-13-0011",
language = "English",
volume = "19",
pages = "4706--4716",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "17",

}

TY - JOUR

T1 - The ubiquitin-CXCR4 axis plays an important role in acute lung infection-enhanced lung tumor metastasis

AU - Yan, Libo

AU - Cai, Qingchun

AU - Xu, Yan

PY - 2013/9/1

Y1 - 2013/9/1

N2 - Purpose: Our goals were to test the effect of acute lung infection on tumor metastasis and to investigate the underlying mechanisms. Experimental Design: Wecombined bacteria-induced and lipopolysaccharide (LPS)-induced acute lung injury/inflammation (ALI) mouse models with mouse metastatic models to study the effect of acute inflammation on lung metastasis in mice. The mechanisms were investigated in ex vivo, in vitro, and in vivo studies. Results: Both bacteria- and LPS-induced ALI significantly enhanced lung metastasis of four tail vein- injected mouse tumor cell lines. Bacteria also enhanced lung metastasis when 4T1 cells were orthotopically injected. The bronchoalveolar lavage fluid (BALF) from LPS- or bacteria-injected mice stimulated migration of tumor cells. In vivo tracking of metastatic RM-9 cells showed that bacterial injection enhanced early dissemination of tumor cells to the lung. The majority of the BALF migratory activity could be blocked by AMD3100, a chemokine receptor 4 (CXCR4) inhibitor. All tested cell lines expressed CXCR4. The levels of extracellular ubiquitin, but not stromal cell-derived factor-1, in BALF were significantly increased by LPS. Ubiquitin was able to induce AMD3100-sensitive migration of tumor cells. Finally, the antibacterial agent amoxicillin and the CXCR4 inhibitor AMD3100 blocked the enhancement effect of bacterial infection on tumor metastasis. Conclusions: Acute lung infection dramatically increased cancer cell homing to the lung and lung metastasis. This change may be due to an alteration of the lung microenvironment and preparation of a favorable metastatic "niche." This effect was seen in multiple cancer types and thus may have broad applications for cancer patients in prevention and/or treatment of metastasis.

AB - Purpose: Our goals were to test the effect of acute lung infection on tumor metastasis and to investigate the underlying mechanisms. Experimental Design: Wecombined bacteria-induced and lipopolysaccharide (LPS)-induced acute lung injury/inflammation (ALI) mouse models with mouse metastatic models to study the effect of acute inflammation on lung metastasis in mice. The mechanisms were investigated in ex vivo, in vitro, and in vivo studies. Results: Both bacteria- and LPS-induced ALI significantly enhanced lung metastasis of four tail vein- injected mouse tumor cell lines. Bacteria also enhanced lung metastasis when 4T1 cells were orthotopically injected. The bronchoalveolar lavage fluid (BALF) from LPS- or bacteria-injected mice stimulated migration of tumor cells. In vivo tracking of metastatic RM-9 cells showed that bacterial injection enhanced early dissemination of tumor cells to the lung. The majority of the BALF migratory activity could be blocked by AMD3100, a chemokine receptor 4 (CXCR4) inhibitor. All tested cell lines expressed CXCR4. The levels of extracellular ubiquitin, but not stromal cell-derived factor-1, in BALF were significantly increased by LPS. Ubiquitin was able to induce AMD3100-sensitive migration of tumor cells. Finally, the antibacterial agent amoxicillin and the CXCR4 inhibitor AMD3100 blocked the enhancement effect of bacterial infection on tumor metastasis. Conclusions: Acute lung infection dramatically increased cancer cell homing to the lung and lung metastasis. This change may be due to an alteration of the lung microenvironment and preparation of a favorable metastatic "niche." This effect was seen in multiple cancer types and thus may have broad applications for cancer patients in prevention and/or treatment of metastasis.

UR - http://www.scopus.com/inward/record.url?scp=84883475479&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84883475479&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-13-0011

DO - 10.1158/1078-0432.CCR-13-0011

M3 - Article

C2 - 23690484

AN - SCOPUS:84883475479

VL - 19

SP - 4706

EP - 4716

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 17

ER -