早期研究發(fā)現(xiàn)趨化因子CXCL10和RANKL具有促進破骨細(xì)胞分化和溶骨性骨轉(zhuǎn)移作用,，但在這些過程中,，內(nèi)源性CXCL10的功能卻未得到研究。
近日,，發(fā)表在Cancer Research雜志上的一則新研究中,，研究人員揭示了內(nèi)源性CXCL10對招募癌細(xì)胞至骨非常重要，能促進破骨細(xì)胞分化,，是形成溶骨性骨轉(zhuǎn)移的關(guān)鍵因子,。
用中和抗體抑制CXCL10能降低遷移癌癥細(xì)胞表達(dá)CXCL10的受體——CXCR3,，CXCL10的缺失能減少體內(nèi)骨腫瘤的負(fù)荷。腫瘤骨骼定向轉(zhuǎn)移過程中宿主CXCL10的產(chǎn)生對癌細(xì)胞的生長和隨后的溶骨是必須的,。腫瘤細(xì)胞和巨噬細(xì)胞之間的直接互動進一步激發(fā)了巨噬細(xì)胞CXCL10的產(chǎn)生,。骨骼轉(zhuǎn)移腫瘤細(xì)胞的生長借助于CXCL10刺激癌細(xì)胞粘附I型膠原以及RANKL介導(dǎo)的破骨細(xì)胞的形成。
總之,，研究結(jié)果證實CXCL10有助于表達(dá)CXCR3的癌細(xì)胞轉(zhuǎn)移至骨,，能促進破骨細(xì)胞的分化。 （生物谷：Bioon.com）
doi:10.1158/0008-5472.CAN-12-0481
PMC:
PMID:
CXCL10 Promotes Osteolytic Bone Metastasis by Enhancing Cancer Outgrowth and Osteoclastogenesis
Jong-Ho Lee, Ha-Neui Kim, Kyung-Ok Kim, Won Jong Jin, Seungbok Lee, Hong-Hee Kim, Hyunil Ha, and Zang Hee Lee
Amplification of the chemokines CXCL10 and RANKL has been suggested to promote osteoclast differentiation and osteolytic bone metastasis, but a function for endogenous CXCL10 in these processes is not well established. In this study, we show that endogenous CXCL10 is critical to recruit cancer cells to bone, support osteoclast differentiation and promote for the formation of osteolytic bone metastases. Neutralizing CXCL10 antibody reduced migration of cancer cells expressing the CXCL10 receptor CXCR3, and loss of CXCR3 or CXCL10 decreased bone tumor burden in vivo. Bone colonization augmented host production of CXCL10, which was required for cancer growth and subsequent osteolysis. Direct interactions between cancer cells and macrophages further stimulated CXCL10 production from macrophages. Growth of bone metastases required CXCL10-stimulated adhesion of cancer cells to type I collagen as well as RANKL-mediated osteoclast formation. Together, our findings show that CXCL10 facilitates trafficking of CXCR3-expressing cancer cells to bone, which augments its own production and promotes osteoclastic differentiation. CXCL10 therefore may represent a therapeutic target for osteolytic bone metastasis.
