Department of Thyroid Surgery, The Affiliated Hospital of Qingdao University Medical College, QingDao University, China.
Eur Rev Med Pharmacol Sci. 2013 Feb;17(4):427-35.
Collagenase-3 (MMP-13), a matrix metalloproteinase, is a recently identified member of the matrix metalloproteinases (MMPs) with broad substrate specificity, and a potential role in tumor metastasis and invasion has been proposed. Collagenase-3 expression has been reported in many carcinomas. However, the presence and possible implication of MMP-13 in the progression of papillary thyroid carcinomas are unknown.
In the present study, we examined MMP-13 gene expression in 208 papillary thyroid carcinomas who underwent surgery without preoperative treatment and 100 matched samples of adjacent normal thyroid tissue (Paraffin-embedded tissue samples) by immunohistochemistry analysis. In vitro and in vivo studies were done in order to investigate the effect of MMP-13 overexpression or silencing on cancer cells invasion and metastasis.
We found MMP-13 expression was significantly increased in the tumours from local regional lymph node metastases patients. The MMP-13 was stained more intensely in invading fronts than in central portions of local regional lymph node. No MMP-13 staining was observed in matched samples of adjacent normal thyroid tissue. MMP-13 expression was significantly related with TNM and recurrent disease, no relation was found with age extent of tumour and size of tumour. Studies with cell and mice models indicated that overexpression of MMP-13 increased cell migration and promoted metastasis, and MMP-13 sliencing decreased cell migration.
The data suggest that MMP-13 is associated with thyroid tumour invasion and metastasis and it may be a potential target for therapeutic intervention.
胶原酶 3(MMP-13)是一种基质金属蛋白酶,是基质金属蛋白酶(MMPs)中最近被鉴定的成员,具有广泛的底物特异性,并被提出在肿瘤转移和侵袭中具有潜在作用。胶原酶 3 的表达已在许多癌中报道。然而,MMP-13 在甲状腺乳头状癌进展中的存在和可能的意义尚不清楚。
本研究通过免疫组织化学分析,检测了 208 例未经术前治疗的甲状腺乳头状癌患者和 100 例配对的正常甲状腺组织(石蜡包埋组织样本)中的 MMP-13 基因表达。为了研究 MMP-13 过表达或沉默对癌细胞侵袭和转移的影响,进行了体外和体内研究。
我们发现 MMP-13 在局部区域淋巴结转移患者的肿瘤中表达显著增加。MMP-13 在局部区域淋巴结的侵袭前沿染色比中央部分更强烈。在配对的正常甲状腺组织样本中未观察到 MMP-13 染色。MMP-13 表达与 TNM 和复发病例显著相关,与年龄、肿瘤范围和肿瘤大小无关。细胞和小鼠模型研究表明,MMP-13 的过表达增加了细胞迁移并促进了转移,而 MMP-13 的沉默减少了细胞迁移。
数据表明 MMP-13 与甲状腺肿瘤的侵袭和转移有关,它可能是治疗干预的潜在靶点。