Analysis of a bone metastasis gene expression signature in patients with bone metastasis from solid tumors
Analysis of a bone metastasis gene expression signature in patients with bone metastasis from solid tumors
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DOI：
10.1007/s10585-011-9438-0
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发表时间：
2012-02-01
影响因子：
4
通讯作者：
Costa, Luis
中科院分区：
文献类型：
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作者：
Casimiro, Sandra;Luis, Ines;Costa, Luis
骨是最常见的实体瘤转移的主要靶点，其导致严重的并发症并且是疼痛的主要原因。在小鼠模型中使用人乳腺癌细胞鉴定骨转移基因表达特征。骨转移相关基因编码与骨归巢（CXCR 4）、血管生成（CTGF和FGF 5）、侵袭（MMP-1和ADAMTS 1）和破骨细胞募集（IL 11）有关的分泌和细胞表面蛋白。该特征叠加在乳腺癌的70个基因不良预后基因表达特征上，并且仅发现ADAMTS 1、CTGF和IL 11在具有骨复发的人原发性乳腺癌中过表达。我们分析了6个骨转移相关基因在不同类型实体瘤患者骨转移中的表达，以评估其在人类临床样本中的相关性。MMP-1，CXCR 4，FGF 5和CTGF被发现在人骨转移的肿瘤细胞中过表达，当与人正常上皮细胞系相比时。与正常乳腺组织相比，所有分析的基因在乳腺癌骨转移的肿瘤细胞中过表达。我们没有检测到这些基因在乳腺癌或其他类型实体瘤骨转移中的表达有任何差异。重要的是，IL 11/CTGF、IL 11/ADAMTS 1、CTGF/CXCR 4、CTGF/ADAMTS 1和MMP-1/ADAMTS 1的表达之间存在显著相关性，支持这些蛋白在骨微环境中的协同功能，以及这些基因在体内骨转移建立中的潜在功能作用。
Bone is a major target for metastases in the most frequent solid tumors, which result in severe complications and are a major cause of pain. A bone metastasis gene expression signature was identified using human breast cancer cells in a mouse model. The bone metastasis-related genes encode secretory and cell surface proteins implicated in bone-homing (CXCR4), angiogenesis (CTGF and FGF5), invasion (MMP-1 and ADAMTS1), and osteoclast recruitment (IL11). This signature superimposes on the 70-gene poor prognosis gene expression signature for breast cancer, and only ADAMTS1, CTGF and IL11 were found to be overexpressed in human primary breast cancers with bone relapse. We analyzed the expression of the six bone metastasis-related genes in bone metastases from patients with different types of solid tumors, to assess its relevance in human clinical samples. MMP-1, CXCR4, FGF5 and CTGF were found to be overexpressed in tumor cells of human bone metastases when compared to a human normal epithelial cell line. All the analyzed genes were overexpressed in the tumor cells of breast cancer bone metastases when compared to normal breast tissue. We did not detect any differences between the expression of these genes in bone metastases from breast cancer or from other types of solid tumors. Importantly, there was a significant correlation between the expressions of IL11/CTGF, IL11/ADAMTS1, CTGF/CXCR4, CTGF/ADAMTS1, and MMP-1/ADAMTS1, supporting the cooperative function of these proteins in the bone microenvironment, and the potential functional role of these genes in the establishment of bone metastases in vivo.