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迪克科夫-1 (DKK-1) 对前列腺癌生长和骨转移的作用

Shiyu Yuan^1,2, Nathan K Hoggard², Noriko Kantake²

¹Department of Biological Sciences, The Molecular and Cellular Biology Program, College of Arts and Sciences, Ohio University, Athens, OH 45701, USA.

|December 9, 2023

概括

Dickkopf-1 (DKK-1) 通过改变信号通路,促进前列腺癌 (PCa) 骨转移的生长和迁移. 虽然DKK-1增加了癌症的进展,但矛盾的是,它减少了骨的形成,这表明它是一个治疗目标.

科学领域:

癌症生物学癌症生物学
在瘤学瘤学.
骨转移研究骨转移研究

背景情况:

骨质母细胞骨转移在晚期前列腺癌 (PCa) 中很常见,增加了死亡率.
迪克科夫-1 (DKK-1) 对抗WNT/β-catenin信号传递,在骨转移中起着复杂的作用.

研究的目的:

探索癌细胞特异性DKK-1在PCa生长,转移和癌症与骨相互作用中的功能.
为了研究DKK-1对PCa骨转移中标准WNT独立途径的影响.

主要方法:

利用一条骨质母细胞PCa细胞系 (Probasco) 并将其注射到无细胞裸体小鼠中.
用人DKK-1 (Probasco + DKK-1) 或没有DKK-1的Probasco细胞注入小鼠骨或心室.
使用生物发光成像,微型CT和组织病理学评估骨转移;在体外评估细胞功能和信号通路.

主要成果:

DKK-1增强了PCa的生长和迁移,独立于正规的WNT信号,增加了增殖和上皮细胞到介质细胞的过渡.
DKK-1通过调节非正规的WNT/JNK信号来对NF-kB/p65信号进行上调,并通过降低非正规的WNT/JNK信号来抑制细胞亡.
DKK-1减弱了骨质细胞活性,导致骨形成减少,并通过OPG/RANKL比率改变了骨质细胞/骨质细胞活性.

结论:

特定于癌细胞的DKK-1促进PCa骨转移的生长和通过WNT独立途径的迁移.
DKK-1通过抑制骨质细胞分化和刺激骨质细胞活性来减少转移的骨诱导.
DKK-1 是治疗前列腺癌骨转移的有希望的治疗点.

关键词:

丹麦克朗 - - 1元狗类犬类动物狗类犬类狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗狗骨质细胞骨转移骨质细胞骨转移前列腺癌是前列腺癌.

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