Filou Serafula, Korpetinou Aggeliki, Kyriakopoulou Dora, Bounias Dimitrios, Stavropoulos Michael, Ravazoula Panagiota, Papachristou Dionysios J, Theocharis Achilleas D, Vynios Demitrios H
Biochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece.
Department of Surgery, School of Health Sciences and University Hospital of Patras, Patras, Greece.
PLoS One. 2015 Mar 18;10(3):e0121209. doi: 10.1371/journal.pone.0121209. eCollection 2015.
ADAMTSs are a family of secreted proteinases that share the metalloproteinase domain with matrix metalloproteinases (MMPs). By acting on a large panel of extracellular substrates, they control several cell functions such as fusion, adhesion, proliferation and migration. Through their thrombospondin motifs they also possess anti-angiogenic properties. We investigated whether ADAMTSs participate in colorectal cancer progression and invasion. Their expression was investigated at both mRNA and protein levels. Using RT-PCR, the expression of ADAMTS-1, -4, -5 and ADAMTS-20 was estimated in colorectal tumors of different cancer stage and anatomic site and 3 cell lines of different aggressiveness. An overexpression of ADAMTS-4 and -5 was observed, especially in tissue samples, whereas ADAMTS-1 and -20 were found to be down-regulated. Western blot analysis further supported the RT-PCR findings, revealing in addition the degradation of ADAMTS-1 and -20 in cancer. In situ expression and localization of ADAMTS-1, -4, -5 and -20 was also investigated by immunohistochemical analysis. Our data suggest a positive correlation between ADAMTS-4 and -5 expression and cancer progression, in contrast with the anti-angiogenic members of the family, ADAMTS-1 and -20, which were found to be down-regulated. Our findings support the notion that overexpression of ADAMTS-4 and ADAMTS-5 in colorectal cancer might be a possible invasive mechanism of cancer cells in order to degrade proteoglycans of ECM.
含血小板反应蛋白基序的解聚素样金属蛋白酶（ADAMTSs）是一类分泌型蛋白酶家族，与基质金属蛋白酶（MMPs）共享金属蛋白酶结构域。通过作用于大量细胞外底物，它们控制多种细胞功能，如融合、黏附、增殖和迁移。通过其血小板反应蛋白基序，它们还具有抗血管生成特性。我们研究了ADAMTSs是否参与结直肠癌的进展和侵袭。在mRNA和蛋白质水平对它们的表达进行了研究。使用逆转录聚合酶链反应（RT-PCR），估计了不同癌症分期和解剖部位的结直肠癌肿瘤以及3种不同侵袭性的细胞系中ADAMTS-1、-4、-5和ADAMTS-20的表达。观察到ADAMTS-4和-5的过表达，尤其是在组织样本中，而ADAMTS-1和-20被发现下调。蛋白质印迹分析进一步支持了RT-PCR的结果，此外还揭示了癌症中ADAMTS-1和-20的降解。还通过免疫组织化学分析研究了ADAMTS-1、-4、-5和-20的原位表达和定位。我们的数据表明，ADAMTS-4和-5的表达与癌症进展呈正相关，这与该家族的抗血管生成成员ADAMTS-1和-20被发现下调形成对比。我们的研究结果支持这样一种观点，即结直肠癌中ADAMTS-4和ADAMTS-5的过表达可能是癌细胞降解细胞外基质蛋白聚糖的一种可能的侵袭机制。
