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Cancer Res:抑制半乳糖凝集素-1治疗胰腺癌

来源:生物谷 2014-07-02 09:11

2014年7月2日讯 /生物谷BIOON/--近日,研究人员已经发现了一种蛋白质--半乳糖凝集素1可作为胰腺癌可能的治疗靶点。第一次,研究人员已经证明此蛋白在胰腺癌小鼠有治疗作用,结果表明能导致小鼠存活率增加20%。这项工作进一步表明,半乳糖凝集素1可能是无不良影响的治疗靶点。

到目前为止,用于治疗胰腺癌的策略是攻击肿瘤细胞,但收效甚微。最新的研究表明,摧毁包围着肿瘤的结构即细胞外基质可能是一个更好的策略。

据了解,半乳糖凝集素1在正常胰腺中没有被发现,但在胰腺肿瘤中强烈表达。此外,一些研究表明半乳糖凝集素-1和肿瘤进展之间有关系。新研究也观察到,消除小鼠体内半乳糖凝集素-1没有有害的后果,这表明它可能是一个安全的治疗靶标,没有不利影响。

他们观察到肿瘤没有半乳糖凝集素-1后,肿瘤显示出更少的增殖,血管减少,更少的炎症和免疫应答增加。所有这些变化都导致肿瘤侵略性较小。(生物谷Bioon.com)

Galectin-1 Drives Pancreatic Carcinogenesis through Stroma Remodeling and Hedgehog Signaling Activation

Neus Martínez-Bosch, et al.

Despite some advances, pancreatic ductal adenocarcinoma (PDAC) remains generally refractory to current treatments. Desmoplastic stroma, a consistent hallmark of PDAC, has emerged as a major source of therapeutic resistance and thus potentially promising targets for improved treatment. The glycan-binding protein galectin-1 (Gal1) is highly expressed in PDAC stroma, but its roles there have not been studied. Here we report functions and molecular pathways of Gal1 that mediate its oncogenic properties in this setting. Genetic ablation of Gal1 in a mouse model of PDAC (EIa-myc mice) dampened tumor progression by inhibiting proliferation, angiogenesis, desmoplasic reaction and by stimulating a tumor-associated immune response, yielding a 20% increase in relative lifesplan. Cellular analyses in vitro and in vivo suggested these effects were mediated through the tumor microenvironment. Importantly, acinar-to-ductal metaplasia, a crucial step for initiation of PDAC, was found to be regulated by Gal1. Mechanistic investigations revealed that Gal1 promoted Hedgehog pathway signaling in PDAC cells and stromal fibroblasts as well as in Ela-myc tumors. Taken together, our findings establish a function for Gal1 in tumor-stroma crosstalk in PDAC and provide a preclinical rationale for Gal1 targeting as a microenvironment-based therapeutic strategy. Cancer Res; 74(13); 3512–24. ?2014 AACR.

 

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