Ninjurin1 inhibits colitis-mediated colon cancer development and growth by suppression of macrophage infiltration through repression of FAK signaling

Jong Kyu Woo, Yeong Su Jang, Ju Hee Kang, Jong-Ik Hwang, Je Kyung Seong, Sang Jin Lee, Sejin Jeon, Goo Taeg Oh, Ho Young Lee, Seung Hyun Oh

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Macrophage infiltration promotes tumorigenesis. However, the macrophage infiltration regulatory molecules have not been fully determined. Nerve injury-induced protein 1 (ninjurin1) is a homophilic cell surface adhesion molecule that plays an important role in cell migration and attachment. Although ninjurin1 is believed to play a role in several malignancies, it is unclear whether ninjurin1 expression contributes to cancer progression. We used transgenic mice (tg mice) that overexpressed ninjurin1 on macrophages. We subjected ninjurin1 tg mice to a well-known mouse model of colitis-associated colon cancer in which animals are treated with azoxymethane (AOM) and dextran sulfate sodium (DSS). After AOM and DSS treatment, ninjurin1 tg mice developed fewer and smaller tumors compared with wild-type (wt) mice. Ninjurin1 tg mice also showed reduced infiltration of macrophages and suppressed angiogenesis in the tumor mass. We therefore explored whether ninjurin1 decreases macrophage migration into the tumor sites. After adoptive transfer to tumor-bearing recipients, wild type and ninjurin1 tg mice's peritoneal macrophages were freshly isolated and labeled with carboxyfluorescein succinimidyl ester (CFSE). As expected, compared with that of wt type macrophages, tumor infiltration of ninjurin1-overexpressing macrophages was significantly decreased. We also found that ninjurin1 overexpression suppressed FAK activity. In addition, knockdown of ninjurin1 enhanced FAK activity and migration activity of RAW264.7 cells. Ninjurin1 overexpression on macrophage inhibits tumor growth by suppression of macrophage infiltration through repression of FAK signaling. Ninjurin1 is a key regulator molecule for macrophage migration and Tumor-associated macrophages (TAM) mediated tumorigenesis in vivo.

Original languageEnglish
Pages (from-to)29592-29604
Number of pages13
JournalOncotarget
Volume7
Issue number20
DOIs
Publication statusPublished - 2016 May 17

Fingerprint

Colitis
Growth and Development
Colonic Neoplasms
Macrophages
Wounds and Injuries
Proteins
Neoplasms
Transgenic Mice
Azoxymethane
Dextran Sulfate
Carcinogenesis
Adoptive Transfer
Cell Adhesion Molecules
Peritoneal Macrophages
Cell Movement
Esters

Keywords

  • Colitis-associated colon cancer model (CAC)
  • Colon cancer
  • Focal adhesion kinase (FAK)
  • Macrophage
  • Ninjurin1

ASJC Scopus subject areas

  • Oncology

Cite this

Ninjurin1 inhibits colitis-mediated colon cancer development and growth by suppression of macrophage infiltration through repression of FAK signaling. / Woo, Jong Kyu; Jang, Yeong Su; Kang, Ju Hee; Hwang, Jong-Ik; Seong, Je Kyung; Lee, Sang Jin; Jeon, Sejin; Oh, Goo Taeg; Lee, Ho Young; Oh, Seung Hyun.

In: Oncotarget, Vol. 7, No. 20, 17.05.2016, p. 29592-29604.

Research output: Contribution to journalArticle

Woo, Jong Kyu ; Jang, Yeong Su ; Kang, Ju Hee ; Hwang, Jong-Ik ; Seong, Je Kyung ; Lee, Sang Jin ; Jeon, Sejin ; Oh, Goo Taeg ; Lee, Ho Young ; Oh, Seung Hyun. / Ninjurin1 inhibits colitis-mediated colon cancer development and growth by suppression of macrophage infiltration through repression of FAK signaling. In: Oncotarget. 2016 ; Vol. 7, No. 20. pp. 29592-29604.
@article{6220704d5a4942e7b39405650d5e222b,
title = "Ninjurin1 inhibits colitis-mediated colon cancer development and growth by suppression of macrophage infiltration through repression of FAK signaling",
abstract = "Macrophage infiltration promotes tumorigenesis. However, the macrophage infiltration regulatory molecules have not been fully determined. Nerve injury-induced protein 1 (ninjurin1) is a homophilic cell surface adhesion molecule that plays an important role in cell migration and attachment. Although ninjurin1 is believed to play a role in several malignancies, it is unclear whether ninjurin1 expression contributes to cancer progression. We used transgenic mice (tg mice) that overexpressed ninjurin1 on macrophages. We subjected ninjurin1 tg mice to a well-known mouse model of colitis-associated colon cancer in which animals are treated with azoxymethane (AOM) and dextran sulfate sodium (DSS). After AOM and DSS treatment, ninjurin1 tg mice developed fewer and smaller tumors compared with wild-type (wt) mice. Ninjurin1 tg mice also showed reduced infiltration of macrophages and suppressed angiogenesis in the tumor mass. We therefore explored whether ninjurin1 decreases macrophage migration into the tumor sites. After adoptive transfer to tumor-bearing recipients, wild type and ninjurin1 tg mice's peritoneal macrophages were freshly isolated and labeled with carboxyfluorescein succinimidyl ester (CFSE). As expected, compared with that of wt type macrophages, tumor infiltration of ninjurin1-overexpressing macrophages was significantly decreased. We also found that ninjurin1 overexpression suppressed FAK activity. In addition, knockdown of ninjurin1 enhanced FAK activity and migration activity of RAW264.7 cells. Ninjurin1 overexpression on macrophage inhibits tumor growth by suppression of macrophage infiltration through repression of FAK signaling. Ninjurin1 is a key regulator molecule for macrophage migration and Tumor-associated macrophages (TAM) mediated tumorigenesis in vivo.",
keywords = "Colitis-associated colon cancer model (CAC), Colon cancer, Focal adhesion kinase (FAK), Macrophage, Ninjurin1",
author = "Woo, {Jong Kyu} and Jang, {Yeong Su} and Kang, {Ju Hee} and Jong-Ik Hwang and Seong, {Je Kyung} and Lee, {Sang Jin} and Sejin Jeon and Oh, {Goo Taeg} and Lee, {Ho Young} and Oh, {Seung Hyun}",
year = "2016",
month = "5",
day = "17",
doi = "10.18632/oncotarget.9020",
language = "English",
volume = "7",
pages = "29592--29604",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "20",

}

TY - JOUR

T1 - Ninjurin1 inhibits colitis-mediated colon cancer development and growth by suppression of macrophage infiltration through repression of FAK signaling

AU - Woo, Jong Kyu

AU - Jang, Yeong Su

AU - Kang, Ju Hee

AU - Hwang, Jong-Ik

AU - Seong, Je Kyung

AU - Lee, Sang Jin

AU - Jeon, Sejin

AU - Oh, Goo Taeg

AU - Lee, Ho Young

AU - Oh, Seung Hyun

PY - 2016/5/17

Y1 - 2016/5/17

N2 - Macrophage infiltration promotes tumorigenesis. However, the macrophage infiltration regulatory molecules have not been fully determined. Nerve injury-induced protein 1 (ninjurin1) is a homophilic cell surface adhesion molecule that plays an important role in cell migration and attachment. Although ninjurin1 is believed to play a role in several malignancies, it is unclear whether ninjurin1 expression contributes to cancer progression. We used transgenic mice (tg mice) that overexpressed ninjurin1 on macrophages. We subjected ninjurin1 tg mice to a well-known mouse model of colitis-associated colon cancer in which animals are treated with azoxymethane (AOM) and dextran sulfate sodium (DSS). After AOM and DSS treatment, ninjurin1 tg mice developed fewer and smaller tumors compared with wild-type (wt) mice. Ninjurin1 tg mice also showed reduced infiltration of macrophages and suppressed angiogenesis in the tumor mass. We therefore explored whether ninjurin1 decreases macrophage migration into the tumor sites. After adoptive transfer to tumor-bearing recipients, wild type and ninjurin1 tg mice's peritoneal macrophages were freshly isolated and labeled with carboxyfluorescein succinimidyl ester (CFSE). As expected, compared with that of wt type macrophages, tumor infiltration of ninjurin1-overexpressing macrophages was significantly decreased. We also found that ninjurin1 overexpression suppressed FAK activity. In addition, knockdown of ninjurin1 enhanced FAK activity and migration activity of RAW264.7 cells. Ninjurin1 overexpression on macrophage inhibits tumor growth by suppression of macrophage infiltration through repression of FAK signaling. Ninjurin1 is a key regulator molecule for macrophage migration and Tumor-associated macrophages (TAM) mediated tumorigenesis in vivo.

AB - Macrophage infiltration promotes tumorigenesis. However, the macrophage infiltration regulatory molecules have not been fully determined. Nerve injury-induced protein 1 (ninjurin1) is a homophilic cell surface adhesion molecule that plays an important role in cell migration and attachment. Although ninjurin1 is believed to play a role in several malignancies, it is unclear whether ninjurin1 expression contributes to cancer progression. We used transgenic mice (tg mice) that overexpressed ninjurin1 on macrophages. We subjected ninjurin1 tg mice to a well-known mouse model of colitis-associated colon cancer in which animals are treated with azoxymethane (AOM) and dextran sulfate sodium (DSS). After AOM and DSS treatment, ninjurin1 tg mice developed fewer and smaller tumors compared with wild-type (wt) mice. Ninjurin1 tg mice also showed reduced infiltration of macrophages and suppressed angiogenesis in the tumor mass. We therefore explored whether ninjurin1 decreases macrophage migration into the tumor sites. After adoptive transfer to tumor-bearing recipients, wild type and ninjurin1 tg mice's peritoneal macrophages were freshly isolated and labeled with carboxyfluorescein succinimidyl ester (CFSE). As expected, compared with that of wt type macrophages, tumor infiltration of ninjurin1-overexpressing macrophages was significantly decreased. We also found that ninjurin1 overexpression suppressed FAK activity. In addition, knockdown of ninjurin1 enhanced FAK activity and migration activity of RAW264.7 cells. Ninjurin1 overexpression on macrophage inhibits tumor growth by suppression of macrophage infiltration through repression of FAK signaling. Ninjurin1 is a key regulator molecule for macrophage migration and Tumor-associated macrophages (TAM) mediated tumorigenesis in vivo.

KW - Colitis-associated colon cancer model (CAC)

KW - Colon cancer

KW - Focal adhesion kinase (FAK)

KW - Macrophage

KW - Ninjurin1

UR - http://www.scopus.com/inward/record.url?scp=84969792023&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84969792023&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.9020

DO - 10.18632/oncotarget.9020

M3 - Article

C2 - 27127177

AN - SCOPUS:84969792023

VL - 7

SP - 29592

EP - 29604

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 20

ER -