Strong expression of CXCL12 is associated with a favorable outcome in osteosarcoma
Strong expression of CXCL12 is associated with a favorable outcome in osteosarcoma
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DOI：
10.1038/modpathol.2011.193
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发表时间：
2012-04-01
期刊：
影响因子：
7.5
通讯作者：
Nathrath, Michaela
中科院分区：
文献类型：
--
作者：
Baumhoer, Daniel;Smida, Jan;Nathrath, Michaela
骨肉瘤的血行播散决定了骨肉瘤的预后，但骨肉瘤血行播散的发生机制尚不清楚。趋化因子是细胞运输和粘附的关键调节因子，并且已经报道了其异常表达，并且与几种恶性肿瘤的不利预后和转移扩散相关。趋化因子受体CXCR 4和CXCR 7与它们的共同配体CXCL 12一起形成在这种情况下最重要的趋化因子轴之一。为了研究这些趋化因子在OS中的潜在作用，我们分析了它们在一系列223个良好表征和治疗前OS样本中的表达。有趣的是，我们发现CXCL 12和CXCR 4的表达与更好的长期结局和更低的转移发生率相关。这些发现表明CXCR 4/CXCR 7/CXCL 12信号在骨肿瘤中具有独特的作用，正如之前在急性白血病中所描述的那样。由于许多恶性肿瘤转移到骨，并且肿瘤细胞被认为响应于CXCL 12而定向到骨，因此表达CXCL 12和相应受体的OS细胞可能被滞留在其起源部位。因此，CXCR 4/CXCR 7/CXCL 12信号传导的破坏可能在OS中对于肿瘤细胞从骨迁移到循环和发展全身性疾病至关重要。Modern Pathology（2012）25，522-528; doi：10.1038/modpathol.2011.193; 2011年12月16日在线发表
Hematogenous spread determines the outcome of osteosarcoma (OS) patients, but the pathogenesis of developing metastatic disease is still unclear. Chemokines are critical regulators of cell trafficking and adhesion, and have been reported to be aberrantly expressed and to correlate with an unfavorable prognosis and metastatic spread in several malignant tumors. The chemokine receptors CXCR4 and CXCR7 together with their common ligand CXCL12 form one of the most important chemokine axes in this context. To investigate a potential role of these chemokines in OSs, we analyzed their expression in a series of 223 well-characterized and pretherapeutic OS samples. Interestingly, we found the expression of CXCL12 and CXCR4 to correlate with a better long-term outcome and with a lower prevalence of metastases. These findings suggest a distinct role of CXCR4/CXCR7/CXCL12 signaling in the tumors of bone, as has also been previously described in acute leukemia. As many malignant tumors metastasize to bone, and tumor cells are thought to be directed to bone in response to CXCL12, OS cells expressing both CXCL12 and the corresponding receptors might be detained at their site of origin. The disruption of CXCR4/CXCR7/CXCL12 signaling could therefore be crucial in OSs for the migration of tumor cells from bone into circulation and for developing systemic disease. Modern Pathology (2012) 25, 522-528; doi:10.1038/modpathol.2011.193; published online 16 December 2011