Zushi Yusuke, Noguchi Kazuma, Hashitani Susumu, Sakurai Kazunari, Segawa Emi, Takaoka Kazuki, Toyohara Yukiyo, Tanaka Noriaki, Kishimoto Hiromitsu, Urade Masahiro
Department of Oral and Maxillofacial Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
Int J Oncol. 2008 Dec;33(6):1133-9.
Adenoid cystic carcinoma (ACC) may acquire a chemokine-mediated mechanism during the process of metastasis. To investigate the involvement of chemokines in metastasis from ACC, expression of CXCR4 in surgical specimens of ACC and two tumor lines transplantable to nude mice was examined immunohistochemically. In addition, the expression levels of CXCR4 protein and mRNA were examined by Western blotting and reverse-transcription polymerase chain reaction. Our results showed that patients whose tumors expressed high levels of CXCR4 had metastases to the regional lymph nodes and the lung, resulting in poor outcomes. ACCs showing a solid or cribriform pattern with distant metastasis were strongly positive for CXCR4, while those showing a tubular or cribriform pattern without metastasis were weakly positive for CXCR4. In the in vivo model, ACCY tumor showed increasing expression levels of CXCR4 with tumor growth, and the histological pattern changed from cribriform to solid. The histological pattern of ACCI, associated with spontaneous metastasis to the neck, changed from cribriform to undifferentiated carcinoma and was highly metastatic to the lung. This tumor showed high levels of CXCR4 protein and mRNA. These results suggest that CXCR4 expression, histological patterns, and metastatic potential are closely related in ACC.
腺样囊性癌（ACC）在转移过程中可能获得一种趋化因子介导的机制。为了研究趋化因子在ACC转移中的作用，采用免疫组织化学方法检测了ACC手术标本及两种可移植到裸鼠的肿瘤细胞系中CXCR4的表达。此外，通过蛋白质印迹法和逆转录聚合酶链反应检测了CXCR4蛋白和mRNA的表达水平。我们的结果显示，肿瘤表达高水平CXCR4的患者出现区域淋巴结和肺转移，预后较差。呈现实性或筛状结构且有远处转移的ACC对CXCR4呈强阳性，而呈现管状或筛状结构且无转移的ACC对CXCR4呈弱阳性。在体内模型中，ACCY肿瘤随着肿瘤生长CXCR4表达水平升高，组织学模式从筛状变为实性。与颈部自发转移相关的ACCI的组织学模式从筛状变为未分化癌，且肺转移率高。该肿瘤显示高水平的CXCR4蛋白和mRNA。这些结果表明，ACC中CXCR4表达、组织学模式和转移潜能密切相关。
