CD44v6 regulates growth of brain tumor stem cells partially through the AKT-mediated pathway.
Identification of stem cell-like brain tumor cells (brain tumor stem-like cells; BTSC) has gained substantial attention by scientists and physicians. However, the mechanism of tumor initiation and proliferation is still poorly understood. CD44 is a cell surface protein linked to tumorigenesis in var...
Main Authors: | , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2011-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3167830?pdf=render |
id |
doaj-021a9cd0b3f2486ebcc191e4ebd9cf03 |
---|---|
record_format |
Article |
spelling |
doaj-021a9cd0b3f2486ebcc191e4ebd9cf032020-11-25T01:44:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0169e2421710.1371/journal.pone.0024217CD44v6 regulates growth of brain tumor stem cells partially through the AKT-mediated pathway.Mayumi JijiwaHabibe DemirSnehalata GuptaCrystal LeungKaushal JoshiNicholas OrozcoTiffany HuangVedat O YildizIchiyo ShibaharaJason A de JesusWilliam H YongPaul S MischelSoledad FernandezHarley I KornblumIchiro NakanoIdentification of stem cell-like brain tumor cells (brain tumor stem-like cells; BTSC) has gained substantial attention by scientists and physicians. However, the mechanism of tumor initiation and proliferation is still poorly understood. CD44 is a cell surface protein linked to tumorigenesis in various cancers. In particular, one of its variant isoforms, CD44v6, is associated with several cancer types. To date its expression and function in BTSC is yet to be identified. Here, we demonstrate the presence and function of the variant form 6 of CD44 (CD44v6) in BTSC of a subset of glioblastoma multiforme (GBM). Patients with CD44(high) GBM exhibited significantly poorer prognoses. Among various variant forms, CD44v6 was the only isoform that was detected in BTSC and its knockdown inhibited in vitro growth of BTSC from CD44(high) GBM but not from CD44(low) GBM. In contrast, this siRNA-mediated growth inhibition was not apparent in the matched GBM sample that does not possess stem-like properties. Stimulation with a CD44v6 ligand, osteopontin (OPN), increased expression of phosphorylated AKT in CD44(high) GBM, but not in CD44(low) GBM. Lastly, in a mouse spontaneous intracranial tumor model, CD44v6 was abundantly expressed by tumor precursors, in contrast to no detectable CD44v6 expression in normal neural precursors. Furthermore, overexpression of mouse CD44v6 or OPN, but not its dominant negative form, resulted in enhanced growth of the mouse tumor stem-like cells in vitro. Collectively, these data indicate that a subset of GBM expresses high CD44 in BTSC, and its growth may depend on CD44v6/AKT pathway.http://europepmc.org/articles/PMC3167830?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mayumi Jijiwa Habibe Demir Snehalata Gupta Crystal Leung Kaushal Joshi Nicholas Orozco Tiffany Huang Vedat O Yildiz Ichiyo Shibahara Jason A de Jesus William H Yong Paul S Mischel Soledad Fernandez Harley I Kornblum Ichiro Nakano |
spellingShingle |
Mayumi Jijiwa Habibe Demir Snehalata Gupta Crystal Leung Kaushal Joshi Nicholas Orozco Tiffany Huang Vedat O Yildiz Ichiyo Shibahara Jason A de Jesus William H Yong Paul S Mischel Soledad Fernandez Harley I Kornblum Ichiro Nakano CD44v6 regulates growth of brain tumor stem cells partially through the AKT-mediated pathway. PLoS ONE |
author_facet |
Mayumi Jijiwa Habibe Demir Snehalata Gupta Crystal Leung Kaushal Joshi Nicholas Orozco Tiffany Huang Vedat O Yildiz Ichiyo Shibahara Jason A de Jesus William H Yong Paul S Mischel Soledad Fernandez Harley I Kornblum Ichiro Nakano |
author_sort |
Mayumi Jijiwa |
title |
CD44v6 regulates growth of brain tumor stem cells partially through the AKT-mediated pathway. |
title_short |
CD44v6 regulates growth of brain tumor stem cells partially through the AKT-mediated pathway. |
title_full |
CD44v6 regulates growth of brain tumor stem cells partially through the AKT-mediated pathway. |
title_fullStr |
CD44v6 regulates growth of brain tumor stem cells partially through the AKT-mediated pathway. |
title_full_unstemmed |
CD44v6 regulates growth of brain tumor stem cells partially through the AKT-mediated pathway. |
title_sort |
cd44v6 regulates growth of brain tumor stem cells partially through the akt-mediated pathway. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2011-01-01 |
description |
Identification of stem cell-like brain tumor cells (brain tumor stem-like cells; BTSC) has gained substantial attention by scientists and physicians. However, the mechanism of tumor initiation and proliferation is still poorly understood. CD44 is a cell surface protein linked to tumorigenesis in various cancers. In particular, one of its variant isoforms, CD44v6, is associated with several cancer types. To date its expression and function in BTSC is yet to be identified. Here, we demonstrate the presence and function of the variant form 6 of CD44 (CD44v6) in BTSC of a subset of glioblastoma multiforme (GBM). Patients with CD44(high) GBM exhibited significantly poorer prognoses. Among various variant forms, CD44v6 was the only isoform that was detected in BTSC and its knockdown inhibited in vitro growth of BTSC from CD44(high) GBM but not from CD44(low) GBM. In contrast, this siRNA-mediated growth inhibition was not apparent in the matched GBM sample that does not possess stem-like properties. Stimulation with a CD44v6 ligand, osteopontin (OPN), increased expression of phosphorylated AKT in CD44(high) GBM, but not in CD44(low) GBM. Lastly, in a mouse spontaneous intracranial tumor model, CD44v6 was abundantly expressed by tumor precursors, in contrast to no detectable CD44v6 expression in normal neural precursors. Furthermore, overexpression of mouse CD44v6 or OPN, but not its dominant negative form, resulted in enhanced growth of the mouse tumor stem-like cells in vitro. Collectively, these data indicate that a subset of GBM expresses high CD44 in BTSC, and its growth may depend on CD44v6/AKT pathway. |
url |
http://europepmc.org/articles/PMC3167830?pdf=render |
work_keys_str_mv |
AT mayumijijiwa cd44v6regulatesgrowthofbraintumorstemcellspartiallythroughtheaktmediatedpathway AT habibedemir cd44v6regulatesgrowthofbraintumorstemcellspartiallythroughtheaktmediatedpathway AT snehalatagupta cd44v6regulatesgrowthofbraintumorstemcellspartiallythroughtheaktmediatedpathway AT crystalleung cd44v6regulatesgrowthofbraintumorstemcellspartiallythroughtheaktmediatedpathway AT kaushaljoshi cd44v6regulatesgrowthofbraintumorstemcellspartiallythroughtheaktmediatedpathway AT nicholasorozco cd44v6regulatesgrowthofbraintumorstemcellspartiallythroughtheaktmediatedpathway AT tiffanyhuang cd44v6regulatesgrowthofbraintumorstemcellspartiallythroughtheaktmediatedpathway AT vedatoyildiz cd44v6regulatesgrowthofbraintumorstemcellspartiallythroughtheaktmediatedpathway AT ichiyoshibahara cd44v6regulatesgrowthofbraintumorstemcellspartiallythroughtheaktmediatedpathway AT jasonadejesus cd44v6regulatesgrowthofbraintumorstemcellspartiallythroughtheaktmediatedpathway AT williamhyong cd44v6regulatesgrowthofbraintumorstemcellspartiallythroughtheaktmediatedpathway AT paulsmischel cd44v6regulatesgrowthofbraintumorstemcellspartiallythroughtheaktmediatedpathway AT soledadfernandez cd44v6regulatesgrowthofbraintumorstemcellspartiallythroughtheaktmediatedpathway AT harleyikornblum cd44v6regulatesgrowthofbraintumorstemcellspartiallythroughtheaktmediatedpathway AT ichironakano cd44v6regulatesgrowthofbraintumorstemcellspartiallythroughtheaktmediatedpathway |
_version_ |
1725028265258647552 |