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

• Published in: Cancer science Vol. 115; no. 4; pp. 1241 - 1249
• Main Authors: Yamanaka, Takahiro, Araki, Kenichiro, Yokobori, Takehiko, Muranushi, Ryo, Hoshino, Kouki, Hagiwara, Kei, Gantumur, Dolgormaa, Ishii, Norihiro, Tsukagoshi, Mariko, Watanabe, Akira, Harimoto, Norifumi, Masamune, Atsushi, Uojima, Haruki, Mizokami, Masashi, Ito, Kiyoaki, Shirabe, Ken
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 01.04.2024
• Subjects: Animals; Antigens, Neoplasm - metabolism; Biomarkers; cancer‐associated fibroblasts; Carcinoma, Hepatocellular - drug therapy; galectin‐3; Gemcitabine; Humans; Liver Cirrhosis; Liver Neoplasms - drug therapy; Mac‐2‐binding protein glycan isomer; Mice; Original; ORIGINAL ARTICLES; pancreatic cancer; Pancreatic Neoplasms - drug therapy; stroma cells; pancreatic cancer; galectin‐3; stroma cells; Mac‐2‐binding protein glycan isomer; cancer‐associated fibroblasts
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/cas.16087

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. Mac‐2‐binding protein glycan isomer (M2BPGi) is primarily secreted by cancer‐associated fibroblasts of pancreatic cancer (PC). M2BPGi promotes the aggressiveness of PC cells. The suppression of M2BP reduced tumor growth and enhanced gemcitabine sensitivity in PC‐bearing xenograft mice.