Potential of Mac-2-binding protein glycan isomer as a new therapeutic target in pancreatic cancer

Takahiro Yamanaka; Kenichiro Araki; Takehiko Yokobori; Ryo Muranushi; Kouki Hoshino; Kei Hagiwara; Dolgormaa Gantumur; Norihiro Ishii; Mariko Tsukagoshi; Akira Watanabe; Norifumi Harimoto; Atsushi Masamune; Haruki Uojima; Masashi Mizokami; Kiyoaki Ito; Ken Shirabe

doi:10.1111/cas.16087

Potential of Mac-2-binding protein glycan isomer as a new therapeutic target in pancreatic cancer

Takahiro Yamanaka, Kenichiro Araki^*, Takehiko Yokobori, Ryo Muranushi, Kouki Hoshino, Kei Hagiwara, Dolgormaa Gantumur, Norihiro Ishii, Mariko Tsukagoshi, Akira Watanabe, Norifumi Harimoto, Atsushi Masamune, Haruki Uojima, Masashi Mizokami, Kiyoaki Ito, Ken Shirabe

^*Corresponding author for this work

Department of Surgery & Science

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

Pancreatic cancer (PC) is a challenging malignancy to treat. Mac-2-binding protein glycan isomer (M2BPGi) is a novel serum marker of liver fibrosis and hepatocellular carcinoma and is secreted by hepatic stellate and stroma cells. Serum M2BPGi levels are upregulated in PC patients. We measured the expression of M2BPGi in the serum of 27 PC patients and determined whether M2BPGi affects the malignant potential of PC cells in vitro. We also examined the effect of M2BP on PC tumor growth and gemcitabine sensitivity in vivo. Serum M2BPGi levels in PC patients were higher compared with those of healthy subjects. M2BPGi extraction in cancer-associated fibroblasts (CAFs) was higher compared with that of PC cells. M2BPGi treatment promoted the proliferation and invasion of PC cells. The suppression of galectin-3, which binds to M2BPGi, did not affect the proliferation-promoting effect of M2BPGi in PC cells. The suppression of M2BP reduced tumor growth and enhanced gemcitabine sensitivity in PC-bearing xenograft mice. CAF-derived M2BPGi promotes the proliferation and invasion of PC cells. Targeting M2BPGi may represent a new therapeutic strategy to circumvent refractory PC.

Original language	English
Pages (from-to)	1241-1249
Number of pages	9
Journal	Cancer Science
Volume	115
Issue number	4
DOIs	https://doi.org/10.1111/cas.16087
State	Published - 2024/04

Keywords

Mac-2-binding protein glycan isomer
cancer-associated fibroblasts
galectin-3
pancreatic cancer
stroma cells

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/cas.16087

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Yamanaka, T., Araki, K., Yokobori, T., Muranushi, R., Hoshino, K., Hagiwara, K., Gantumur, D., Ishii, N., Tsukagoshi, M., Watanabe, A., Harimoto, N., Masamune, A., Uojima, H., Mizokami, M., Ito, K., & Shirabe, K. (2024). Potential of Mac-2-binding protein glycan isomer as a new therapeutic target in pancreatic cancer. Cancer Science, 115(4), 1241-1249. https://doi.org/10.1111/cas.16087

@article{4e79765935ba43198806d1556392bfae,

title = "Potential of Mac-2-binding protein glycan isomer as a new therapeutic target in pancreatic cancer",

abstract = "Pancreatic cancer (PC) is a challenging malignancy to treat. Mac-2-binding protein glycan isomer (M2BPGi) is a novel serum marker of liver fibrosis and hepatocellular carcinoma and is secreted by hepatic stellate and stroma cells. Serum M2BPGi levels are upregulated in PC patients. We measured the expression of M2BPGi in the serum of 27 PC patients and determined whether M2BPGi affects the malignant potential of PC cells in vitro. We also examined the effect of M2BP on PC tumor growth and gemcitabine sensitivity in vivo. Serum M2BPGi levels in PC patients were higher compared with those of healthy subjects. M2BPGi extraction in cancer-associated fibroblasts (CAFs) was higher compared with that of PC cells. M2BPGi treatment promoted the proliferation and invasion of PC cells. The suppression of galectin-3, which binds to M2BPGi, did not affect the proliferation-promoting effect of M2BPGi in PC cells. The suppression of M2BP reduced tumor growth and enhanced gemcitabine sensitivity in PC-bearing xenograft mice. CAF-derived M2BPGi promotes the proliferation and invasion of PC cells. Targeting M2BPGi may represent a new therapeutic strategy to circumvent refractory PC.",

keywords = "Mac-2-binding protein glycan isomer, cancer-associated fibroblasts, galectin-3, pancreatic cancer, stroma cells",

author = "Takahiro Yamanaka and Kenichiro Araki and Takehiko Yokobori and Ryo Muranushi and Kouki Hoshino and Kei Hagiwara and Dolgormaa Gantumur and Norihiro Ishii and Mariko Tsukagoshi and Akira Watanabe and Norifumi Harimoto and Atsushi Masamune and Haruki Uojima and Masashi Mizokami and Kiyoaki Ito and Ken Shirabe",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.",

year = "2024",

month = apr,

doi = "10.1111/cas.16087",

language = "英語",

volume = "115",

pages = "1241--1249",

journal = "Cancer Science",

issn = "1347-9032",

publisher = "Wiley-Blackwell",

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Yamanaka, T, Araki, K, Yokobori, T, Muranushi, R, Hoshino, K, Hagiwara, K, Gantumur, D, Ishii, N, Tsukagoshi, M, Watanabe, A, Harimoto, N, Masamune, A, Uojima, H, Mizokami, M, Ito, K & Shirabe, K 2024, 'Potential of Mac-2-binding protein glycan isomer as a new therapeutic target in pancreatic cancer', Cancer Science, vol. 115, no. 4, pp. 1241-1249. https://doi.org/10.1111/cas.16087

TY - JOUR

T1 - Potential of Mac-2-binding protein glycan isomer as a new therapeutic target in pancreatic cancer

AU - Yamanaka, Takahiro

AU - Araki, Kenichiro

AU - Yokobori, Takehiko

AU - Muranushi, Ryo

AU - Hoshino, Kouki

AU - Hagiwara, Kei

AU - Gantumur, Dolgormaa

AU - Ishii, Norihiro

AU - Tsukagoshi, Mariko

AU - Watanabe, Akira

AU - Harimoto, Norifumi

AU - Masamune, Atsushi

AU - Uojima, Haruki

AU - Mizokami, Masashi

AU - Ito, Kiyoaki

AU - Shirabe, Ken

PY - 2024/4

Y1 - 2024/4

N2 - Pancreatic cancer (PC) is a challenging malignancy to treat. Mac-2-binding protein glycan isomer (M2BPGi) is a novel serum marker of liver fibrosis and hepatocellular carcinoma and is secreted by hepatic stellate and stroma cells. Serum M2BPGi levels are upregulated in PC patients. We measured the expression of M2BPGi in the serum of 27 PC patients and determined whether M2BPGi affects the malignant potential of PC cells in vitro. We also examined the effect of M2BP on PC tumor growth and gemcitabine sensitivity in vivo. Serum M2BPGi levels in PC patients were higher compared with those of healthy subjects. M2BPGi extraction in cancer-associated fibroblasts (CAFs) was higher compared with that of PC cells. M2BPGi treatment promoted the proliferation and invasion of PC cells. The suppression of galectin-3, which binds to M2BPGi, did not affect the proliferation-promoting effect of M2BPGi in PC cells. The suppression of M2BP reduced tumor growth and enhanced gemcitabine sensitivity in PC-bearing xenograft mice. CAF-derived M2BPGi promotes the proliferation and invasion of PC cells. Targeting M2BPGi may represent a new therapeutic strategy to circumvent refractory PC.

AB - Pancreatic cancer (PC) is a challenging malignancy to treat. Mac-2-binding protein glycan isomer (M2BPGi) is a novel serum marker of liver fibrosis and hepatocellular carcinoma and is secreted by hepatic stellate and stroma cells. Serum M2BPGi levels are upregulated in PC patients. We measured the expression of M2BPGi in the serum of 27 PC patients and determined whether M2BPGi affects the malignant potential of PC cells in vitro. We also examined the effect of M2BP on PC tumor growth and gemcitabine sensitivity in vivo. Serum M2BPGi levels in PC patients were higher compared with those of healthy subjects. M2BPGi extraction in cancer-associated fibroblasts (CAFs) was higher compared with that of PC cells. M2BPGi treatment promoted the proliferation and invasion of PC cells. The suppression of galectin-3, which binds to M2BPGi, did not affect the proliferation-promoting effect of M2BPGi in PC cells. The suppression of M2BP reduced tumor growth and enhanced gemcitabine sensitivity in PC-bearing xenograft mice. CAF-derived M2BPGi promotes the proliferation and invasion of PC cells. Targeting M2BPGi may represent a new therapeutic strategy to circumvent refractory PC.

KW - Mac-2-binding protein glycan isomer

KW - cancer-associated fibroblasts

KW - galectin-3

KW - pancreatic cancer

KW - stroma cells

UR - http://www.scopus.com/inward/record.url?scp=85184405114&partnerID=8YFLogxK

U2 - 10.1111/cas.16087

DO - 10.1111/cas.16087

M3 - 学術論文

C2 - 38321872

AN - SCOPUS:85184405114

SN - 1347-9032

VL - 115

SP - 1241

EP - 1249

JO - Cancer Science

JF - Cancer Science

IS - 4

ER -

Potential of Mac-2-binding protein glycan isomer as a new therapeutic target in pancreatic cancer

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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