乳腺癌細(xì)胞經(jīng)常從腫瘤原位組織侵入骨骼,，導(dǎo)致病人的生存機(jī)會(huì)減少,。這個(gè)轉(zhuǎn)移過程是非常復(fù)雜的，乳腺癌細(xì)胞本身和骨環(huán)境等在這一過程中都發(fā)揮重要作用,。近日,，一項(xiàng)發(fā)表在Journal of Biological Chemistry雜志上的由西班牙生物醫(yī)學(xué)研究所的研究人員完成的一項(xiàng)研究分析了乳腺癌細(xì)胞移植到骨的具體機(jī)制。
研究人員重點(diǎn)研究了骨骼發(fā)育中發(fā)揮重要作用的基因NOG,。此前,，NOG與前列腺癌骨轉(zhuǎn)移的關(guān)聯(lián)已有所研究，但其在乳腺癌骨轉(zhuǎn)移中的具體作用仍不清楚,。
Gomis和同事們研究發(fā)現(xiàn),，一旦乳腺癌細(xì)胞啟動(dòng)NOG，乳腺癌細(xì)胞就會(huì)侵入骨,，并建立新的腫瘤轉(zhuǎn)移灶,。首先，NOG會(huì)增加一些成熟的破骨細(xì)胞的數(shù)量,。第二,，NOG保持轉(zhuǎn)移性乳腺癌細(xì)胞的干細(xì)胞樣的狀態(tài)，這使腫瘤細(xì)胞能夠傳播和形成新的腫瘤轉(zhuǎn)移灶,。
Gomis解釋：NOG表達(dá)增加乳腺癌骨轉(zhuǎn)移的作用是因?yàn)樗粌H影響侵略性癌癥細(xì)胞固有的本能（如建立新腫瘤轉(zhuǎn)移灶的能力）,，而且還影響骨骼環(huán)境（如導(dǎo)致破骨細(xì)胞變性），在這兩方面共同促進(jìn)乳腺癌的骨轉(zhuǎn)移,。（生物谷：Bioon.com）
doi:10.1074/jbc.M112.355834
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Identification of NOG as a specific breast cancer bone metastasis-supporting gene.
Tarragona M, Pavlovic M, Arnal-Estape A, Urosevic J, Morales M, Guiu M, Planet E, Gonzalez-Suarez E, Gomis RR.
Metastasis requires numerous biological functions that jointly provide tumor cells from a primary site to seed and colonize a distant organ. Some of these activities are selected for in the primary site while others are acquired at the metastatic niche. We provide molecular evidence showing that the BMP inhibitor, NOG, provide metastatic breast cancer cells with the ability to colonize the bone. NOG expression is acquired during the late events of metastasis, once cells have departed from the primary site, since it is not enriched in primary tumors with high risk of bone relapse. Contrary, breast cancer bone metastatic lesions do select for high levels of NOG expression compared to metastasis to the lung, liver and brain. Pivotal to the bone colonization functions is the contribution of NOG to metastatic autonomous and non-autonomous cell functions. Using genetic approaches, we show that when NOG is expressed in human breast cancer cells facilitates bone colonization by fostering osteoclast differentiation, bone degradation and also contributes to metastatic lesions re-initiation. These findings reveal how aggressive cancer cell autonomous and non-autonomous functions can be mechanistically coupled to greater bone metastatic potential.
