Fish oil prevents breast cancer cell metastasis to bone.
Fish oil prevents breast cancer cell metastasis to bone.
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DOI：
10.1016/j.bbrc.2010.10.063
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发表时间：
2010-11-26
影响因子：
3.1
通讯作者：
Ghosh-Choudhury N
中科院分区：
文献类型：
--
作者：
Mandal CC;Ghosh-Choudhury T;Yoneda T;Choudhury GG;Ghosh-Choudhury N
来自流行病学和动物模型的数据证实了鱼油（富含 ω-3 多不饱和脂肪酸）对改善肿瘤生长和进展（包括乳腺癌）的有益作用。乳腺癌患者经常出现骨转移，表现为溶骨性病变，导致剧烈疼痛和骨折。使用 MDA-MB-231 人乳腺癌细胞骨转移的小鼠模型，我们表明富含 DHA（二十二碳六烯酸）和 EPA（二十碳五烯酸）的鱼油饮食可以防止骨中溶骨性病变的形成，表明可以抑制癌细胞骨转移。这些结果得到了我们的数据的支持，显示 DHA 和 EPA 均显着减弱培养物中 MDA-MB-231 乳腺癌细胞的迁移/侵袭。迄今为止，限制乳腺癌细胞选择性转移至骨的机制仍未被探索。 CD44 表达异常增加与癌症干细胞的产生有关，从而促进乳腺癌细胞的转移。我们证明 DHA 和 EPA 通过转录机制显着抑制 CD44 蛋白和 mRNA 的表达。此外，我们发现，与对照饮食相比，喂食鱼油饮食的小鼠肿瘤中 CD44 mRNA 和蛋白质的水平显着降低。我们的数据提供了第一个证据，证明鱼油对乳腺癌骨转移具有有益作用。我们的结果确定了鱼油活性成分 DHA 和 EPA 的新功能，它们靶向细胞内在促转移分子 CD44 来抑制迁移/侵袭。
The data derived from epidemiological and animal models confirm a beneficial effect of fish oil (rich in ω-3 polyunsaturated fatty acids) in the amelioration of tumor growth and progression, including breast cancer. The breast cancer patients often develop bone metastasis evidenced by osteolytic lesions, leading to severe pain and bone fracture. Using a mouse model of MDA-MB-231 human breast cancer cell metastasis to bone, here we show that fish oil diet enriched in DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) prevents the formation of osteolytic lesions in bone, indicating suppression of cancer cell metastasis to bone. These results are supported by our data showing both DHA and EPA significantly attenuate the migration/invasion of MDA-MB-231 breast cancer cells in culture. The mechanism that limits breast cancer cells to selective metastasis to bone remains hitherto unexplored. Aberrant increased expression of CD44 is associated with generation of cancer stem cells, which contribute to metastasis of breast cancer cells. We demonstrate that DHA and EPA significantly inhibit the expression of CD44 protein and mRNA by a transcriptional mechanism. Furthermore, we show markedly reduced levels of CD44 mRNA and protein in the tumors of mice, which were fed fish oil diet than those in control diet. Our data provide the first evidence for a salutary effect of fish oil on breast cancer metastasis to bone. Our results identify a novel function of the fish oil active components, DHA and EPA, which target the cell-intrinsic pro-metastatic molecule CD44 to inhibit migration/invasion.
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影响因子：
64.5
作者：
Godar S;Ince TA;Bell GW;Feldser D;Donaher JL;Bergh J;Liu A;Miu K;Watnick RS;Reinhardt F;McAllister SS;Jacks T;Weinberg RA
通讯作者：
Weinberg RA
影响因子：
4.8
作者：
Ghosh-Choudhury, Nandini;Singha, Prajjal K.;Choudhury, Goutam Ghosh
通讯作者：
Choudhury, Goutam Ghosh
影响因子：
15.9
作者：
Guise, TA;Yin, JJ;Mundy, GR
通讯作者：
Mundy, GR
影响因子：
4.8
作者：
Mandal, Chandi C.;Choudhury, Goutam Ghosh;Ghosh-Choudhury, Nandini
通讯作者：
Ghosh-Choudhury, Nandini
影响因子：
7.1
作者：
LANDS, WEM;HAMAZAKI, T;HUBBARD, VS
通讯作者：
HUBBARD, VS