Fidelity of Runx2 activity in breast cancer cells is required for the generation of metastases-associated osteolytic disease
Fidelity of Runx2 activity in breast cancer cells is required for the generation of metastases-associated osteolytic disease
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DOI：
10.1158/0008-5472.can-03-3851
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发表时间：
2004-07-01
期刊：
影响因子：
11.2
通讯作者：
Gerstenfeld, LC
中科院分区：
文献类型：
--
作者：
Barnes, GL;Hebert, KE;Gerstenfeld, LC
与乳腺癌骨转移相关的溶骨性骨破坏代表了严重且不可治愈的临床病症。然而，调节溶骨性疾病产生中所涉及的因子的肿瘤细胞表达的分子机制仍然难以捉摸。我们最近发现乳腺癌细胞表达Runx2转录因子，这是骨形成和骨骼稳态调节所必需的。我们的实验结果表明，扰动Runx2的调节功能，在肿瘤细胞废除他们的能力，在体内形成溶骨性病变。在体外，我们发现乳腺癌细胞抑制成骨细胞分化，同时增强骨髓基质细胞培养中的破骨细胞分化。Runx2活性的破坏消除了这两种癌细胞介导的对骨细胞的影响。这些结果表明，乳腺癌细胞中的Runx2表达提供了一种分子表型，使肿瘤细胞和骨微环境之间的相互作用，导致溶骨性疾病。
The osteolytic bone destruction associated with breast cancer skeletal metastases represents a serious and incurable clinical condition. However, the molecular mechanisms regulating tumor cell expression of factors involved in the generation of osteolytic disease remain elusive. We demonstrated recently that breast cancer cells express the Runx2 transcription factor, essential for bone formation and a regulator of skeletal homeostasis. Our experimental results demonstrate that perturbation of Runx2 regulatory function in tumor cells abolishes their ability to form osteolytic lesions in vivo. In vitro, we show that breast cancer cells inhibit osteoblast differentiation while concurrently enhancing osteoclast differentiation in marrow stromal cell cultures. Disruption of Runx2 activity abrogates both of these cancer cell-mediated effects on bone cells. These results demonstrate that Runx2 expression in breast cancer cells provides a molecular phenotype that enables the interactions between tumor cells and the bone microenvironment that lead to osteolytic disease.