Inhibition of Lysyl Oxidase and Lysyl Oxidase-Like Enzymes Has Tumour-Promoting and Tumour-Suppressing Roles in Experimental Prostate Cancer.
Inhibition of Lysyl Oxidase and Lysyl Oxidase-Like Enzymes Has Tumour-Promoting and Tumour-Suppressing Roles in Experimental Prostate Cancer.
复制标题
在实验前列腺癌中抑制赖氨酰氧化酶和赖氨酸氧化酶样酶具有肿瘤促进和肿瘤抑制作用。
DOI：
10.1038/srep19608
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发表时间：
2016-01-25
影响因子：
4.6
通讯作者：
Halin Bergström S
中科院分区：
文献类型：
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作者：
Nilsson M;Adamo H;Bergh A;Halin Bergström S
赖氨酸氧化酶（LOX）和LOX样酶（LOXL）是细胞外基质沉积和成熟的关键酶。LOX促进肿瘤进展和转移，但它也可能具有肿瘤抑制作用。本研究表明，原位植入大鼠前列腺AT-1肿瘤细胞增加了肿瘤和周围非恶性前列腺组织中LOX和LOXLs mRNA的表达。在AT-1细胞植入前，使用β -氨基丙腈（BAPN）抑制LOX酶，可减少肿瘤生长。相反，在肿瘤确定后开始治疗，结果是肿瘤生长不受影响或增加。此外，当静脉注射肿瘤细胞时，BAPN治疗并没有抑制自发淋巴结转移的形成，也没有抑制肺肿瘤负荷。在肿瘤和肿瘤邻近的前列腺组织中观察到胶原纤维含量的暂时减少，这是LOX的靶标。这也许可以解释为什么早期的BAPN治疗在抑制肿瘤生长方面比较晚开始的治疗更有效。我们的数据表明，LOX家族的酶功能是环境依赖的，在前列腺癌中具有肿瘤抑制和肿瘤促进特性。需要进一步的研究来了解在何种情况下LOX抑制可能被用作癌症患者的治疗靶点。
Lysyl oxidase (LOX) and LOX-like (LOXL) enzymes are key players in extracellular matrix deposition and maturation. LOX promote tumour progression and metastasis, but it may also have tumour-inhibitory effects. Here we show that orthotopic implantation of rat prostate AT-1 tumour cells increased LOX and LOXLs mRNA expressions in the tumour and in the surrounding non-malignant prostate tissue. Inhibition of LOX enzymes, using Beta-aminopropionitrile (BAPN), initiated before implantation of AT-1 cells, reduced tumour growth. Conversely, treatment that was started after the tumours were established resulted in unaffected or increased tumour growth. Moreover, treatment with BAPN did not suppress the formation of spontaneous lymph node metastases, or lung tumour burden, when tumour cells were injected intravenously. A temporal decrease in collagen fibre content, which is a target for LOX, was observed in tumours and in the tumour-adjacent prostate tissue. This may explain why early BAPN treatment is more effective in inhibiting tumour growth compared to treatment initiated later. Our data suggest that the enzymatic function of the LOX family is context-dependent, with both tumour-suppressing and tumour-promoting properties in prostate cancer. Further investigations are needed to understand the circumstances under which LOX inhibition may be used as a therapeutic target for cancer patients.