The lysyl oxidase inhibitor, beta-aminopropionitrile, diminishes the metastatic colonization potential of circulating breast cancer cells.
The lysyl oxidase inhibitor, beta-aminopropionitrile, diminishes the metastatic colonization potential of circulating breast cancer cells.
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DOI：
10.1371/journal.pone.0005620
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Jirik FR
中科院分区：
文献类型：
--
作者：
Bondareva A;Downey CM;Ayres F;Liu W;Boyd SK;Hallgrimsson B;Jirik FR
赖氨酰氧化酶（LOX），细胞外基质重塑酶，似乎有促进乳腺癌细胞的运动性和侵袭性的作用。此外，LOX表达的增加与乳腺癌患者的无乳腺癌和总生存率的降低相关。在此背景下，我们研究了β-氨基丙腈（BAPN）（LOX的不可逆抑制剂）调节人乳腺癌细胞系MDA-MB-231转移定植潜力的能力。在心内注射表达荧光素酶的MDA-MB-231-Luc 2细胞之前1天、同一天或之后7天开始每天向小鼠施用BAPN。通过体内生物发光成像监测转移的发展，并通过显微计算机断层扫描（μCT）评估肿瘤诱导的骨质溶解。我们发现BAPN给药能够降低转移的频率。因此，当BAPN治疗在心脏内注射肿瘤细胞的前一天或同一天开始时，转移瘤的数量分别减少了44%和27%，全身光子发射率（反映总肿瘤负荷）分别减少了78%和45%。相反，BAPN对已建立的转移瘤的生长没有影响。我们的研究结果表明，LOX活性需要在外渗和/或初始组织定植循环MDA-MB-231细胞，贷款支持的想法，LOX抑制可能是有用的转移预防。
Lysyl oxidase (LOX), an extracellular matrix remodeling enzyme, appears to have a role in promoting breast cancer cell motility and invasiveness. In addition, increased LOX expression has been correlated with decreases in both metastases-free, and overall survival in breast cancer patients. With this background, we studied the ability of β-aminopropionitrile (BAPN), an irreversible inhibitor of LOX, to regulate the metastatic colonization potential of the human breast cancer cell line, MDA-MB-231. BAPN was administered daily to mice starting either 1 day prior, on the same day as, or 7 days after intracardiac injection of luciferase expressing MDA-MB-231-Luc2 cells. Development of metastases was monitored by in vivo bioluminescence imaging, and tumor-induced osteolysis was assessed by micro-computed tomography (μCT). We found that BAPN administration was able to reduce the frequency of metastases. Thus, when BAPN treatment was initiated the day before, or on the same day as the intra-cardiac injection of tumor cells, the number of metastases was decreased by 44%, and 27%, and whole-body photon emission rates (reflective of total tumor burden) were diminished by 78%, and 45%, respectively. In contrast, BAPN had no effect on the growth of established metastases. Our findings suggest that LOX activity is required during extravasation and/or initial tissue colonization by circulating MDA-MB-231 cells, lending support to the idea that LOX inhibition might be useful in metastasis prevention.
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DOI：
10.1186/bcr1026
发表时间：
2005
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Jenkins DE;Hornig YS;Oei Y;Dusich J;Purchio T
通讯作者：
Purchio T
影响因子：
4.8
作者：
Giampuzzi, M;Botti, G;Di Donato, A
通讯作者：
Di Donato, A
影响因子：
4
作者：
Kagan, HM;Li, WD
通讯作者：
Li, WD
影响因子：
4
作者：
Drake, Justin M.;Gabriel, Curtis L.;Henry, Michael D.
通讯作者：
Henry, Michael D.
影响因子：
3.5
作者：
Di Donato, A;Lacal, JC;Gusmano, R
通讯作者：
Gusmano, R