Osteoactivin regulates head and neck squamous cell carcinoma invasion by modulating matrix metalloproteases.
Osteoactivin regulates head and neck squamous cell carcinoma invasion by modulating matrix metalloproteases.
复制标题
DOI：
10.1002/jcp.25900
复制
发表时间：
2018-01
影响因子：
5.6
通讯作者：
Safadi FF
中科院分区：
文献类型：
--
作者：
Arosarena OA;Barr EW;Thorpe R;Yankey H;Tarr JT;Safadi FF
近60%的头颈部鳞状细胞癌（HNSCC）患者死于转移或局部复发。转移由癌细胞迁移和侵袭介导，其部分依赖于基质金属蛋白酶降解细胞外基质。骨激活素（OA）过表达在几种恶性肿瘤的转移中起作用，并已显示上调基质金属蛋白酶（MMP）的表达和活性。确定OA如何调节MMP在HNSCC中的表达和活性，并研究OA对细胞侵袭的影响。我们评估了OA处理对HNSCC细胞系中MMP mRNA和蛋白表达以及明胶酶和酪蛋白溶解活性的影响。我们评估了OA基因沉默对MMP表达、明胶酶和酪蛋白溶解活性以及细胞侵袭的影响。OA处理对MMP mRNA表达有不同影响。OA处理上调了UMSCC 14 a（p=0.0431）和SCC 15（p<0.0001）细胞中的MMP-10表达，但降低了UMSCC 14 a细胞中的MMP-9表达（p=0.0002）。OA基因沉默降低了UMSCC 12细胞中MMP-10的表达（p=0.0001），以及SCC 25细胞中MMP-3（p=0.0005）和MMP-9（p=0.0036）的表达。在SCC 15和SCC 25细胞中，OA处理分别增加MMP-2（p=0.0408）和MMP-9明胶酶活性（p<0.0001）。OA耗竭降低SCC 25细胞中MMP-2（p=0.0023）和MMP-9（p<0.0001）活性。OA处理增加了UMSCC 12细胞中70 kDa的酪蛋白溶解活性，与组织型纤溶酶原激活剂一致（p=0.0078）。OA消耗降低UMSCC 12细胞的侵袭能力（p<0.0001）。OA对HNSCC中MMP表达的影响是可变的，并且可能促进癌细胞侵袭。
Nearly 60% of patients with head and neck squamous cell carcinoma (HNSCC) die of metastases or locoregional recurrence. Metastasis is mediated by cancer cell migration and invasion, which are in part dependent on extracellular matrix degradation by matrix metalloproteinases. Osteoactivin (OA) overexpression plays a role in metastases in several malignancies, and has been shown to upregulate matrix metalloproteinase (MMP) expression and activity. To determine how OA modulates MMP expression and activity in HNSCC, and to investigate OA effects on cell invasion. We assessed effects of OA treatment on MMP mRNA and protein expression, as well as gelatinase and caseinolytic activity in HNSCC cell lines. We assessed the effects of OA gene silencing on MMP expression, gelatinase and caseinolytic activity, and cell invasion. OA treatment had differential effects on MMP mRNA expression. OA treatment upregulated MMP-10 expression in UMSCC14a (p=0.0431) and SCC15 (p<0.0001) cells, but decreased MMP-9 expression in UMSCC14a cells (p=0.0002). OA gene silencing decreased MMP-10 expression in UMSCC12 cells (p=0.0001), and MMP-3 (p=0.0005) and -9 (p=0.0036) expression in SCC25 cells. In SCC15 and SCC25 cells, OA treatment increased MMP-2 (p=0.0408) and MMP-9 gelatinase activity (p<0.0001), respectively. OA depletion decreased MMP-2 (p=0.0023) and -9 (p<0.0001) activity in SCC25 cells. OA treatment increased 70 kDa caseinolytic activity in UMSCC12 cells consistent with tissue type plasminogen activator (p=0.0078). OA depletion decreased invasive capacity of UMSCC12 cells (p<0.0001). OA’s effects on MMP expression in HNSCC are variable, and may promote cancer cell invasion.
登录
查看更多内容
影响因子：
3.7
作者：
Fullar, Alexandra;Kovalszky, Ilona;Bitsche, Mario;Romani, Angela;Schartinger, Volker Hans;Sprinzl, Georg Mathias;Riechelmann, Herbert;Dudas, Jozsef
通讯作者：
Dudas, Jozsef
影响因子：
5.6
作者：
Arosarena, Oneida A.;Del Carpio-Cano, Fabiola E.;Dela Cadena, Raul A.;Rico, Mario C.;Nwodim, Emeka;Safadi, Fayez F.
通讯作者：
Safadi, Fayez F.
DOI：
10.1053/paor.1999.0217
发表时间：
1999-01-01
期刊：
Pathology oncology research : POR
影响因子：
--
作者：
Du, B;Wang, P;Du, B
通讯作者：
Du, B
影响因子：
64.5
作者：
Brooks, PC;Stromblad, S;Cheresh, DA
通讯作者：
Cheresh, DA
影响因子：
9.3
作者：
Gao X;Mi S;Zhang F;Gong F;Lai Y;Gao F;Zhang X;Wang L;Tao H
通讯作者：
Tao H