Demircan Kadir, Gunduz Esra, Gunduz Mehmet, Beder Levent Bekir, Hirohata Satoshi, Nagatsuka Hitoshi, Cengiz Beyhan, Cilek Mehmet Zeynel, Yamanaka Noboru, Shimizu Kenji, Ninomiya Yoshifumi
Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Shikatacho, Okayama, Japan.
Head Neck. 2009 Jun;31(6):793-801. doi: 10.1002/hed.21045.
Although contribution of matrix metalloproteinases in cancer progression and dissemination is now well known, roles of recently discovered metalloproteinases, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), in cancer development and progression remain mostly unknown.
Here we examined the mRNA expression pattern of 6 members of ADAMTS aggrecanases (1, 4, 5, 8, 9, and 15) in primary head and neck cancer with and without metastasis by real-time reverse transcriptase-polymerase chain reaction.
Expression levels of ADAMTS mRNAs were lower in the majority of the primary tumors as compared with the controls. On the other hand, the expression levels of all of the ADAMTS mRNAs except ADAMTS4 were higher in the metastatic foci than in their corresponding primary tumors, which suggest that characteristics of the cancer cell population are different in the primary tumor and metastatic focus.
Our findings suggest a metastasis model proposing accumulation of a subtype of cancer cells with high metastatic capacity within heterogenous primary tumor cell population.
尽管基质金属蛋白酶在癌症进展和扩散中的作用现已广为人知,但最近发现的金属蛋白酶,即具有血小板反应蛋白基序的解聚素和金属蛋白酶(ADAMTS)在癌症发生和发展中的作用仍大多未知。
在此,我们通过实时逆转录聚合酶链反应检测了6种ADAMTS聚糖酶(1、4、5、8、9和15)在有转移和无转移的原发性头颈癌中的mRNA表达模式。
与对照组相比,大多数原发性肿瘤中ADAMTS mRNA的表达水平较低。另一方面,除ADAMTS4外,所有ADAMTS mRNA在转移灶中的表达水平均高于其相应的原发性肿瘤,这表明原发性肿瘤和转移灶中癌细胞群体的特征不同。
我们的研究结果提示了一种转移模型,即在异质性原发性肿瘤细胞群体中,具有高转移能力的癌细胞亚型会发生聚集。