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Integrin α7 and Extracellular Matrix Laminin 211 Interaction Promotes Proliferation of Acute Myeloid Leukemia Cells and Is Associated with Granulocytic Sarcoma

Acute myeloid leukemia (AML) with granulocytic sarcoma (GS) is characterized by poor prognosis; however, its underlying mechanism is unclear. Bone marrow samples from 64 AML patients (9 with GS and 55 without GS) together with AML cell lines PL21, THP1, HL60, Kasumi-1, and KG-1 were used to elucidat...

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Autores principales: Kobayashi, Nobuhiko, Oda, Tsukasa, Takizawa, Makiko, Ishizaki, Takuma, Tsukamoto, Norifumi, Yokohama, Akihiko, Takei, Hisashi, Saitoh, Takayuki, Shimizu, Hiroaki, Honma, Kazuki, Kimura-Masuda, Kei, Kuroda, Yuko, Ishihara, Rei, Murakami, Yuki, Murakami, Hirokazu, Handa, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072541/
https://www.ncbi.nlm.nih.gov/pubmed/32033262
http://dx.doi.org/10.3390/cancers12020363
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author Kobayashi, Nobuhiko
Oda, Tsukasa
Takizawa, Makiko
Ishizaki, Takuma
Tsukamoto, Norifumi
Yokohama, Akihiko
Takei, Hisashi
Saitoh, Takayuki
Shimizu, Hiroaki
Honma, Kazuki
Kimura-Masuda, Kei
Kuroda, Yuko
Ishihara, Rei
Murakami, Yuki
Murakami, Hirokazu
Handa, Hiroshi
author_facet Kobayashi, Nobuhiko
Oda, Tsukasa
Takizawa, Makiko
Ishizaki, Takuma
Tsukamoto, Norifumi
Yokohama, Akihiko
Takei, Hisashi
Saitoh, Takayuki
Shimizu, Hiroaki
Honma, Kazuki
Kimura-Masuda, Kei
Kuroda, Yuko
Ishihara, Rei
Murakami, Yuki
Murakami, Hirokazu
Handa, Hiroshi
author_sort Kobayashi, Nobuhiko
collection PubMed
description Acute myeloid leukemia (AML) with granulocytic sarcoma (GS) is characterized by poor prognosis; however, its underlying mechanism is unclear. Bone marrow samples from 64 AML patients (9 with GS and 55 without GS) together with AML cell lines PL21, THP1, HL60, Kasumi-1, and KG-1 were used to elucidate the pathology of AML with GS. RNA-Seq analyses were performed on samples from seven AML patients with or without GS. Gene set enrichment analyses revealed significantly upregulated candidates on the cell surface of the GS group. Expression of the adhesion integrin α7 (ITGA7) was significantly higher in the GS group, as seen by RT-qPCR (p = 0.00188) and immunohistochemistry of bone marrow formalin-fixed, paraffin-embedded (FFPE) specimens. Flow cytometry revealed enhanced proliferation of PL21 and THP1 cells containing surface ITGA7 in the presence of laminin 211 and stimulated ERK phosphorylation; this effect was abrogated following ITGA7 knockdown or ERK inhibition. Overall, high ITGA7 expression was associated with poor patient survival (p = 0.0477). In summary, ITGA7 is highly expressed in AML with GS, and its ligand (laminin 211) stimulates cell proliferation through ERK signaling. This is the first study demonstrating the role of integrin α7 and extracellular matrix interactions in AML cell proliferation and extramedullary disease development.
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spelling pubmed-70725412020-03-19 Integrin α7 and Extracellular Matrix Laminin 211 Interaction Promotes Proliferation of Acute Myeloid Leukemia Cells and Is Associated with Granulocytic Sarcoma Kobayashi, Nobuhiko Oda, Tsukasa Takizawa, Makiko Ishizaki, Takuma Tsukamoto, Norifumi Yokohama, Akihiko Takei, Hisashi Saitoh, Takayuki Shimizu, Hiroaki Honma, Kazuki Kimura-Masuda, Kei Kuroda, Yuko Ishihara, Rei Murakami, Yuki Murakami, Hirokazu Handa, Hiroshi Cancers (Basel) Article Acute myeloid leukemia (AML) with granulocytic sarcoma (GS) is characterized by poor prognosis; however, its underlying mechanism is unclear. Bone marrow samples from 64 AML patients (9 with GS and 55 without GS) together with AML cell lines PL21, THP1, HL60, Kasumi-1, and KG-1 were used to elucidate the pathology of AML with GS. RNA-Seq analyses were performed on samples from seven AML patients with or without GS. Gene set enrichment analyses revealed significantly upregulated candidates on the cell surface of the GS group. Expression of the adhesion integrin α7 (ITGA7) was significantly higher in the GS group, as seen by RT-qPCR (p = 0.00188) and immunohistochemistry of bone marrow formalin-fixed, paraffin-embedded (FFPE) specimens. Flow cytometry revealed enhanced proliferation of PL21 and THP1 cells containing surface ITGA7 in the presence of laminin 211 and stimulated ERK phosphorylation; this effect was abrogated following ITGA7 knockdown or ERK inhibition. Overall, high ITGA7 expression was associated with poor patient survival (p = 0.0477). In summary, ITGA7 is highly expressed in AML with GS, and its ligand (laminin 211) stimulates cell proliferation through ERK signaling. This is the first study demonstrating the role of integrin α7 and extracellular matrix interactions in AML cell proliferation and extramedullary disease development. MDPI 2020-02-05 /pmc/articles/PMC7072541/ /pubmed/32033262 http://dx.doi.org/10.3390/cancers12020363 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kobayashi, Nobuhiko
Oda, Tsukasa
Takizawa, Makiko
Ishizaki, Takuma
Tsukamoto, Norifumi
Yokohama, Akihiko
Takei, Hisashi
Saitoh, Takayuki
Shimizu, Hiroaki
Honma, Kazuki
Kimura-Masuda, Kei
Kuroda, Yuko
Ishihara, Rei
Murakami, Yuki
Murakami, Hirokazu
Handa, Hiroshi
Integrin α7 and Extracellular Matrix Laminin 211 Interaction Promotes Proliferation of Acute Myeloid Leukemia Cells and Is Associated with Granulocytic Sarcoma
title Integrin α7 and Extracellular Matrix Laminin 211 Interaction Promotes Proliferation of Acute Myeloid Leukemia Cells and Is Associated with Granulocytic Sarcoma
title_full Integrin α7 and Extracellular Matrix Laminin 211 Interaction Promotes Proliferation of Acute Myeloid Leukemia Cells and Is Associated with Granulocytic Sarcoma
title_fullStr Integrin α7 and Extracellular Matrix Laminin 211 Interaction Promotes Proliferation of Acute Myeloid Leukemia Cells and Is Associated with Granulocytic Sarcoma
title_full_unstemmed Integrin α7 and Extracellular Matrix Laminin 211 Interaction Promotes Proliferation of Acute Myeloid Leukemia Cells and Is Associated with Granulocytic Sarcoma
title_short Integrin α7 and Extracellular Matrix Laminin 211 Interaction Promotes Proliferation of Acute Myeloid Leukemia Cells and Is Associated with Granulocytic Sarcoma
title_sort integrin α7 and extracellular matrix laminin 211 interaction promotes proliferation of acute myeloid leukemia cells and is associated with granulocytic sarcoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072541/
https://www.ncbi.nlm.nih.gov/pubmed/32033262
http://dx.doi.org/10.3390/cancers12020363
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