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

被引：18

作者：

Kobayashi, Nobuhiko ^{[1
]}

Oda, Tsukasa ^{[2
]}

Takizawa, Makiko ^{[1
]}

Ishizaki, Takuma ^{[1
]}

Tsukamoto, Norifumi ^{[3
]}

Yokohama, Akihiko ^{[4
]}

Takei, Hisashi ^{[1
]}

Saitoh, Takayuki ^{[5
]}

Shimizu, Hiroaki ^{[1
]}

Honma, Kazuki ^{[5
]}

Kimura-Masuda, Kei ^{[5
]}

Kuroda, Yuko ^{[5
]}

Ishihara, Rei ^{[5
]}

Murakami, Yuki ^{[5
]}

Murakami, Hirokazu ^{[5
]}

Handa, Hiroshi ^{[1
]}

机构：

[1] Gunma Univ, Dept Hematol, Grad Sch Med, Maebashi, Gunma 3718510, Japan

[2] Gunma Univ, Inst Mol & Cellular Regulat, Lab Mol Genet, Maebashi, Gunma 3718510, Japan

[3] Gunma Univ Hosp, Oncol Ctr, Maebashi, Gunma 3718510, Japan

[4] Gunma Univ Hosp, Blood Transfus Serv, Maebashi, Gunma 3718510, Japan

[5] Gunma Univ, Grad Sch Hlth Sci, Maebashi, Gunma 3718510, Japan

来源：

CANCERS | 2020年 / 12卷 / 02期

关键词：

acute myelogenous leukemia; granulocytic sarcoma; integrin; laminin; extracellular matrix; ADULT PATIENTS; EXPRESSION; GROWTH; ISOFORMS; ADHESION; MIGRATION; INVASION; NICHE; ROLES; AML;

D O I：

10.3390/cancers12020363

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 alpha 7 (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 alpha 7 and extracellular matrix interactions in AML cell proliferation and extramedullary disease development.

引用

页数：15

共 64 条

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