Tumoral RANKL activates astrocytes that promote glioma cell invasion through cytokine signaling.

Jun Kyum Kim, Xiong Jin, Young Woo Sohn, Xun Jin, Hee Young Jeon, Eun Jung Kim, Seok Won Ham, Hye Min Jeon, So Young Chang, Se Yeong Oh, Jinlong Yin, Sung Hak Kim, Jong Bae Park, Ichiro Nakano, Hyunggee Kim

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The invasiveness of glioblastoma is a major cause of poor prognosis and relapse. However, the molecular mechanism controlling glioma cell invasion is poorly understood. Here, we report that receptor activator of nuclear factor kappa-B (NFκB) ligand (RANKL) promotes glioma cell invasion in vivo, but not in vitro. Unlike the invasiveness under in vitro culture conditions, in vivo xenograft studies revealed that LN229 cells expressing high endogenous RANKL generated more invasive tumors than U87MG cells expressing relatively low endogenous RANKL. Consistently, RANKL-overexpressing U87MG resulted in invasive tumors, whereas RANKL-depleted LN229 generated rarely invasive tumors. We found that the number of activated astrocytes was markedly increased in the periphery of RANKL-high invasive tumors. RANKL activated astrocytes through NFκB signaling and these astrocytes in turn secreted various factors which regulate glioma cell invasion. Among them, transforming growth factor β (TGF-β) signaling was markedly increased in glioblastoma specimens and xenograft tumors expressing high levels of RANKL. These results indicate that RANKL contributes to glioma invasion by modulating the peripheral microenvironment of the tumor, and that targeting RANKL signaling has important implications for the prevention of highly invasive glioblastoma.

Original languageEnglish
Pages (from-to)194-200
Number of pages7
JournalCancer Letters
Volume353
Issue number2
Publication statusPublished - 2014 Jan 1

Fingerprint

Glioma
Astrocytes
Tumors
Cytokines
Glioblastoma
Neoplasms
Heterografts
RANK Ligand
Cells
Tumor Microenvironment
NF-kappa B
Transforming Growth Factors
Recurrence
In Vitro Techniques

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kim, J. K., Jin, X., Sohn, Y. W., Jin, X., Jeon, H. Y., Kim, E. J., ... Kim, H. (2014). Tumoral RANKL activates astrocytes that promote glioma cell invasion through cytokine signaling. Cancer Letters, 353(2), 194-200.

Tumoral RANKL activates astrocytes that promote glioma cell invasion through cytokine signaling. / Kim, Jun Kyum; Jin, Xiong; Sohn, Young Woo; Jin, Xun; Jeon, Hee Young; Kim, Eun Jung; Ham, Seok Won; Jeon, Hye Min; Chang, So Young; Oh, Se Yeong; Yin, Jinlong; Kim, Sung Hak; Park, Jong Bae; Nakano, Ichiro; Kim, Hyunggee.

In: Cancer Letters, Vol. 353, No. 2, 01.01.2014, p. 194-200.

Research output: Contribution to journalArticle

Kim, JK, Jin, X, Sohn, YW, Jin, X, Jeon, HY, Kim, EJ, Ham, SW, Jeon, HM, Chang, SY, Oh, SY, Yin, J, Kim, SH, Park, JB, Nakano, I & Kim, H 2014, 'Tumoral RANKL activates astrocytes that promote glioma cell invasion through cytokine signaling.', Cancer Letters, vol. 353, no. 2, pp. 194-200.
Kim JK, Jin X, Sohn YW, Jin X, Jeon HY, Kim EJ et al. Tumoral RANKL activates astrocytes that promote glioma cell invasion through cytokine signaling. Cancer Letters. 2014 Jan 1;353(2):194-200.
Kim, Jun Kyum ; Jin, Xiong ; Sohn, Young Woo ; Jin, Xun ; Jeon, Hee Young ; Kim, Eun Jung ; Ham, Seok Won ; Jeon, Hye Min ; Chang, So Young ; Oh, Se Yeong ; Yin, Jinlong ; Kim, Sung Hak ; Park, Jong Bae ; Nakano, Ichiro ; Kim, Hyunggee. / Tumoral RANKL activates astrocytes that promote glioma cell invasion through cytokine signaling. In: Cancer Letters. 2014 ; Vol. 353, No. 2. pp. 194-200.
@article{ad34beb119fa4f2dadfec6fec59a4108,
title = "Tumoral RANKL activates astrocytes that promote glioma cell invasion through cytokine signaling.",
abstract = "The invasiveness of glioblastoma is a major cause of poor prognosis and relapse. However, the molecular mechanism controlling glioma cell invasion is poorly understood. Here, we report that receptor activator of nuclear factor kappa-B (NFκB) ligand (RANKL) promotes glioma cell invasion in vivo, but not in vitro. Unlike the invasiveness under in vitro culture conditions, in vivo xenograft studies revealed that LN229 cells expressing high endogenous RANKL generated more invasive tumors than U87MG cells expressing relatively low endogenous RANKL. Consistently, RANKL-overexpressing U87MG resulted in invasive tumors, whereas RANKL-depleted LN229 generated rarely invasive tumors. We found that the number of activated astrocytes was markedly increased in the periphery of RANKL-high invasive tumors. RANKL activated astrocytes through NFκB signaling and these astrocytes in turn secreted various factors which regulate glioma cell invasion. Among them, transforming growth factor β (TGF-β) signaling was markedly increased in glioblastoma specimens and xenograft tumors expressing high levels of RANKL. These results indicate that RANKL contributes to glioma invasion by modulating the peripheral microenvironment of the tumor, and that targeting RANKL signaling has important implications for the prevention of highly invasive glioblastoma.",
author = "Kim, {Jun Kyum} and Xiong Jin and Sohn, {Young Woo} and Xun Jin and Jeon, {Hee Young} and Kim, {Eun Jung} and Ham, {Seok Won} and Jeon, {Hye Min} and Chang, {So Young} and Oh, {Se Yeong} and Jinlong Yin and Kim, {Sung Hak} and Park, {Jong Bae} and Ichiro Nakano and Hyunggee Kim",
year = "2014",
month = "1",
day = "1",
language = "English",
volume = "353",
pages = "194--200",
journal = "The BMJ",
issn = "0730-6512",
publisher = "Kluwer Academic Publishers",
number = "2",

}

TY - JOUR

T1 - Tumoral RANKL activates astrocytes that promote glioma cell invasion through cytokine signaling.

AU - Kim, Jun Kyum

AU - Jin, Xiong

AU - Sohn, Young Woo

AU - Jin, Xun

AU - Jeon, Hee Young

AU - Kim, Eun Jung

AU - Ham, Seok Won

AU - Jeon, Hye Min

AU - Chang, So Young

AU - Oh, Se Yeong

AU - Yin, Jinlong

AU - Kim, Sung Hak

AU - Park, Jong Bae

AU - Nakano, Ichiro

AU - Kim, Hyunggee

PY - 2014/1/1

Y1 - 2014/1/1

N2 - The invasiveness of glioblastoma is a major cause of poor prognosis and relapse. However, the molecular mechanism controlling glioma cell invasion is poorly understood. Here, we report that receptor activator of nuclear factor kappa-B (NFκB) ligand (RANKL) promotes glioma cell invasion in vivo, but not in vitro. Unlike the invasiveness under in vitro culture conditions, in vivo xenograft studies revealed that LN229 cells expressing high endogenous RANKL generated more invasive tumors than U87MG cells expressing relatively low endogenous RANKL. Consistently, RANKL-overexpressing U87MG resulted in invasive tumors, whereas RANKL-depleted LN229 generated rarely invasive tumors. We found that the number of activated astrocytes was markedly increased in the periphery of RANKL-high invasive tumors. RANKL activated astrocytes through NFκB signaling and these astrocytes in turn secreted various factors which regulate glioma cell invasion. Among them, transforming growth factor β (TGF-β) signaling was markedly increased in glioblastoma specimens and xenograft tumors expressing high levels of RANKL. These results indicate that RANKL contributes to glioma invasion by modulating the peripheral microenvironment of the tumor, and that targeting RANKL signaling has important implications for the prevention of highly invasive glioblastoma.

AB - The invasiveness of glioblastoma is a major cause of poor prognosis and relapse. However, the molecular mechanism controlling glioma cell invasion is poorly understood. Here, we report that receptor activator of nuclear factor kappa-B (NFκB) ligand (RANKL) promotes glioma cell invasion in vivo, but not in vitro. Unlike the invasiveness under in vitro culture conditions, in vivo xenograft studies revealed that LN229 cells expressing high endogenous RANKL generated more invasive tumors than U87MG cells expressing relatively low endogenous RANKL. Consistently, RANKL-overexpressing U87MG resulted in invasive tumors, whereas RANKL-depleted LN229 generated rarely invasive tumors. We found that the number of activated astrocytes was markedly increased in the periphery of RANKL-high invasive tumors. RANKL activated astrocytes through NFκB signaling and these astrocytes in turn secreted various factors which regulate glioma cell invasion. Among them, transforming growth factor β (TGF-β) signaling was markedly increased in glioblastoma specimens and xenograft tumors expressing high levels of RANKL. These results indicate that RANKL contributes to glioma invasion by modulating the peripheral microenvironment of the tumor, and that targeting RANKL signaling has important implications for the prevention of highly invasive glioblastoma.

UR - http://www.scopus.com/inward/record.url?scp=84908668451&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908668451&partnerID=8YFLogxK

M3 - Article

C2 - 25079688

AN - SCOPUS:84908668451

VL - 353

SP - 194

EP - 200

JO - The BMJ

JF - The BMJ

SN - 0730-6512

IS - 2

ER -