Abstract
Anaplastic thyroid carcinoma (ATC) is one of the most lethal carcinoma with a poor prognosis; however, molecular mechanisms underlying the aggressiveness of ATC remain unclear. Our goal was to examine the expression of X-linked inhibitor of apoptosis protein (XIAP) in ATC, as well as its role in ATC tumorigenesis. This is a retrospective study of ATC patients from the Second Affiliated Hospital of Harbin Medical University during June 2003 to October 2013. The expression of XIAP in tumor specimens of ATC patients was examined by immunohistochemical staining. The roles of XIAP in proliferation, migration, invasion, and chemoresistance were investigated by shRNA mediated-knockdown of XIAP in human ATC cell lines. The effect of XIAP on tumorigenesis was evaluated using a xenograft tumor model with nude mice. XIAP expression was significantly higher in the invasive area of ATC samples, whereas XIAP expression was negative in either normal thyroid follicular epithelial cells or the differentiated papillary thyroid carcinoma. XIAP-depleted ATC cells showed a remarkable decrease in the proliferation, migration, and invasion compared with the scramble group. Knockdown of XIAP expression significantly enhanced the chemosensitivity of WRO and SW1736 cells to docetaxel or taxane. Moreover, knockdown of XIAP significantly suppressed ATC tumorigenesis in vivo. XIAP is highly expressed in ATC cells and tumors. XIAP play important roles in tumor behaviors and chemosensitivity of ATC cells. XIAP may function in ATC aggressiveness and may serve as a potential therapeutic target for ATC treatment.
Highlights
Anaplastic thyroid carcinoma (ATC) is a rare and highly aggressive subtype of thyroid malignancy and induces up to 14%–39% of thyroid cancer-related deaths [1]
In vitro experiments showed that X-linked inhibitor of apoptosis protein (XIAP) was expressed in the ATC cell lines WRO and SW1736, whereas, no expression of XIAP was detected in the primary cultured follicular cells or the differentiated thyroid cancer cell lines (Figure 1), indicating that XIAP may serve as a specific biomarker of ATC tumors
Immunohistochemical analysis showed negative XIAP expression in welldifferentiated papillary thyroid carcinoma (PTC) and nodular hyperplasia (Figure 2A), while XIAP was positively expressed in most tumor tissues of ATC patients (n = 12), with abundant staining in membranous
Summary
Anaplastic thyroid carcinoma (ATC) is a rare and highly aggressive subtype of thyroid malignancy and induces up to 14%–39% of thyroid cancer-related deaths [1]. Current treatment strategies fail sometimes due to therapeutic resistance; more effective treatment strategies for ATC are still urgently needed. Aberrant expression of XIAP was found in a variety of human cancers, including esophageal carcinoma, acute leukemia, non-small cell human lung cancer, ovarian carcinoma, bladder cancer, and several other carcinomas [3,4,5,6,7,8]. Increased XIAP expression has been shown to correlate with chemoresistance of cancer cells to drugs and radiotherapy [9, 10]. Whereas, decreased expression of XIAP sensitizes drug-resistance of cancer cells to apoptosis [11, 12]. XIAP may serve as a potential diagnostic and therapeutic target for antineoplastic therapy. We investigated the expression pattern as well as the function of XIAP in ATC
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