Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgical Science, Gunma University, Graduate School of Medicine, Maebashi, Gunma, Japan.
Gunma University Initiative for Advanced Research, Maebashi, Gunma, Japan.
Cancer Sci. 2024 Apr;115(4):1241-1249. doi: 10.1111/cas.16087. Epub 2024 Feb 6.
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.
胰腺癌（PC）是一种难以治疗的恶性肿瘤。M2 结合蛋白糖型异构体（M2BPGi）是肝纤维化和肝细胞癌的新型血清标志物，由肝星状细胞和基质细胞分泌。PC 患者的血清 M2BPGi 水平升高。我们测量了 27 名 PC 患者血清中的 M2BPGi 表达，并确定 M2BPGi 是否会影响 PC 细胞在体外的恶性潜能。我们还研究了 M2BP 对体内 PC 肿瘤生长和吉西他滨敏感性的影响。与健康受试者相比，PC 患者的血清 M2BPGi 水平更高。与 PC 细胞相比，癌症相关成纤维细胞（CAFs）中的 M2BPGi 提取更高。M2BPGi 处理促进了 PC 细胞的增殖和侵袭。与 M2BPGi 结合的半乳糖凝集素-3 的抑制作用并不影响 M2BPGi 在 PC 细胞中的促增殖作用。M2BP 的抑制作用减少了荷瘤异种移植小鼠的肿瘤生长并增强了吉西他滨的敏感性。CAF 衍生的 M2BPGi 促进了 PC 细胞的增殖和侵袭。靶向 M2BPGi 可能代表一种规避难治性 PC 的新治疗策略。
