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Stromal cells expressing hedgehog-interacting protein regulate the proliferation of myeloid neoplasms

Aberrant reactivation of hedgehog (Hh) signaling has been described in a wide variety of human cancers including cancer stem cells. However, involvement of the Hh-signaling system in the bone marrow (BM) microenvironment during the development of myeloid neoplasms is unknown. In this study, we asses...

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Autores principales: Kobune, M, Iyama, S, Kikuchi, S, Horiguchi, H, Sato, T, Murase, K, Kawano, Y, Takada, K, Ono, K, Kamihara, Y, Hayashi, T, Miyanishi, K, Sato, Y, Takimoto, R, Kato, J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461706/
https://www.ncbi.nlm.nih.gov/pubmed/22961059
http://dx.doi.org/10.1038/bcj.2012.36
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author Kobune, M
Iyama, S
Kikuchi, S
Horiguchi, H
Sato, T
Murase, K
Kawano, Y
Takada, K
Ono, K
Kamihara, Y
Hayashi, T
Miyanishi, K
Sato, Y
Takimoto, R
Kato, J
author_facet Kobune, M
Iyama, S
Kikuchi, S
Horiguchi, H
Sato, T
Murase, K
Kawano, Y
Takada, K
Ono, K
Kamihara, Y
Hayashi, T
Miyanishi, K
Sato, Y
Takimoto, R
Kato, J
author_sort Kobune, M
collection PubMed
description Aberrant reactivation of hedgehog (Hh) signaling has been described in a wide variety of human cancers including cancer stem cells. However, involvement of the Hh-signaling system in the bone marrow (BM) microenvironment during the development of myeloid neoplasms is unknown. In this study, we assessed the expression of Hh-related genes in primary human CD34(+) cells, CD34(+) blastic cells and BM stromal cells. Both Indian Hh (Ihh) and its signal transducer, smoothened (SMO), were expressed in CD34(+) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)-derived cells. However, Ihh expression was relatively low in BM stromal cells. Remarkably, expression of the intrinsic Hh-signaling inhibitor, human Hh-interacting protein (HHIP) in AML/MDS-derived stromal cells was markedly lower than in healthy donor-derived stromal cells. Moreover, HHIP expression levels in BM stromal cells highly correlated with their supporting activity for SMO(+) leukemic cells. Knockdown of HHIP gene in stromal cells increased their supporting activity although control cells marginally supported SMO(+) leukemic cell proliferation. The demethylating agent, 5-aza-2′-deoxycytidine rescued HHIP expression via demethylation of HHIP gene and reduced the leukemic cell-supporting activity of AML/MDS-derived stromal cells. This indicates that suppression of stromal HHIP could be associated with the proliferation of AML/MDS cells.
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spelling pubmed-34617062012-10-03 Stromal cells expressing hedgehog-interacting protein regulate the proliferation of myeloid neoplasms Kobune, M Iyama, S Kikuchi, S Horiguchi, H Sato, T Murase, K Kawano, Y Takada, K Ono, K Kamihara, Y Hayashi, T Miyanishi, K Sato, Y Takimoto, R Kato, J Blood Cancer J Original Article Aberrant reactivation of hedgehog (Hh) signaling has been described in a wide variety of human cancers including cancer stem cells. However, involvement of the Hh-signaling system in the bone marrow (BM) microenvironment during the development of myeloid neoplasms is unknown. In this study, we assessed the expression of Hh-related genes in primary human CD34(+) cells, CD34(+) blastic cells and BM stromal cells. Both Indian Hh (Ihh) and its signal transducer, smoothened (SMO), were expressed in CD34(+) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)-derived cells. However, Ihh expression was relatively low in BM stromal cells. Remarkably, expression of the intrinsic Hh-signaling inhibitor, human Hh-interacting protein (HHIP) in AML/MDS-derived stromal cells was markedly lower than in healthy donor-derived stromal cells. Moreover, HHIP expression levels in BM stromal cells highly correlated with their supporting activity for SMO(+) leukemic cells. Knockdown of HHIP gene in stromal cells increased their supporting activity although control cells marginally supported SMO(+) leukemic cell proliferation. The demethylating agent, 5-aza-2′-deoxycytidine rescued HHIP expression via demethylation of HHIP gene and reduced the leukemic cell-supporting activity of AML/MDS-derived stromal cells. This indicates that suppression of stromal HHIP could be associated with the proliferation of AML/MDS cells. Nature Publishing Group 2012-09 2012-09-07 /pmc/articles/PMC3461706/ /pubmed/22961059 http://dx.doi.org/10.1038/bcj.2012.36 Text en Copyright © 2012 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Original Article
Kobune, M
Iyama, S
Kikuchi, S
Horiguchi, H
Sato, T
Murase, K
Kawano, Y
Takada, K
Ono, K
Kamihara, Y
Hayashi, T
Miyanishi, K
Sato, Y
Takimoto, R
Kato, J
Stromal cells expressing hedgehog-interacting protein regulate the proliferation of myeloid neoplasms
title Stromal cells expressing hedgehog-interacting protein regulate the proliferation of myeloid neoplasms
title_full Stromal cells expressing hedgehog-interacting protein regulate the proliferation of myeloid neoplasms
title_fullStr Stromal cells expressing hedgehog-interacting protein regulate the proliferation of myeloid neoplasms
title_full_unstemmed Stromal cells expressing hedgehog-interacting protein regulate the proliferation of myeloid neoplasms
title_short Stromal cells expressing hedgehog-interacting protein regulate the proliferation of myeloid neoplasms
title_sort stromal cells expressing hedgehog-interacting protein regulate the proliferation of myeloid neoplasms
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461706/
https://www.ncbi.nlm.nih.gov/pubmed/22961059
http://dx.doi.org/10.1038/bcj.2012.36
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