Dickkopf-1 (Dkk1) protein expression in breast cancer with special reference to bone metastases
Dickkopf-1 (Dkk1) protein expression in breast cancer with special reference to bone metastases
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DOI：
10.1007/s10585-018-9937-3
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发表时间：
2018-12-01
影响因子：
4
通讯作者：
Solomayer, Erich-Franz
中科院分区：
文献类型：
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作者：
Kasoha, Mariz;Bohle, Rainer M.;Solomayer, Erich-Franz
Wnt抑制剂dickkopf-1蛋白（Dkk 1）的失调已在多种癌症中报道。此外，它还通过损害成骨细胞活性与恶性骨疾病的进展有关。本研究调查了乳腺癌患者血清和组织中Dkk 1的水平-或无骨转移。采用ELISA法检测89例乳腺癌患者和86例健康妇女血清Dkk 1水平。通过免疫组织化学染色在143种不同组织中检测了Dkk 1和β-连环蛋白（Wnt转导途径的主要下游组分）的组织水平，包括邻近的非肿瘤乳腺组织、原发性乳腺肿瘤、淋巴结转移和骨转移。与健康对照组相比，无转移的乳腺癌患者血清Dkk 1水平显著升高，骨转移患者血清Dkk 1水平甚至更高。Dkk 1在70%的乳腺癌组织中表达阳性，并与组织学类型和PR状态显著相关。与邻近的非肿瘤乳腺组织和原发性乳腺肿瘤相比，在淋巴结转移和骨转移中发现Dkk 1的表达频率较低。β-连环蛋白的组织表达在绝大多数测试的组织类型中是阳性的，表明激活的Wnt/β-连环蛋白信号传导。我们的研究结果表明，Wnt/β-catenin信号在乳腺肿瘤及其继发淋巴结和骨转移是失调，这可能与异常Dkk 1表达水平。因此，Dkk 1蛋白可能为乳腺癌及其骨转移的新型综合治疗策略的持续发展提供见解。
Dysregulation of the Wnt inhibitor dickkopf-1 protein (Dkk1) has been reported in a variety of cancers. In addition, it has been linked to the progression of malignant bone disease by impairing osteoblast activity. This study investigated serum- and tissue levels of Dkk1 in breast cancer patients with- or without bone metastases. Serum Dkk1 levels were measured by ELISA in 89 breast cancer patients and 86 healthy women. Tissue levels of Dkk1 and -catenin, a major downstream component of Wnt transduction pathway, were tested with immunohistochemical staining in 143 different tissues, including adjacent non-tumoral breast tissues, primary breast tumours, lymph nodes metastases, and bone metastases. Serum levels of Dkk1 were significantly increased in breast cancer patients without metastases compared with healthy controls and even more increased in patients with bone metastases. Tissue expression of Dkk1 was positive in 70% of tested primary breast cancer tissues and demonstrated significant correlation with histological type and PR status. Less frequent expression of Dkk1 was found in lymph nodes metastases and bone metastases compared with adjacent non-tumoral breast tissues and primary breast tumours. Tissue expression of -catenin was positive in the vast majority of all tested tissue types indicating activated Wnt/-catenin signalling. Our results suggested that Wnt/-catenin signalling in breast tumours and their secondary lymph nodes- and bone metastases is dysregulated and this could be related to aberrant Dkk1 expression levels. Hence, Dkk1 protein might provide insights into the continued development of novel comprehensive and therapeutic strategies for breast cancer and its bone metastases.