Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms.
Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms.
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DOI：
10.18632/oncotarget.3515
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发表时间：
2015-04-20
期刊：
影响因子：
--
通讯作者：
Goldberg GS
中科院分区：
文献类型：
--
作者：
Ochoa-Alvarez JA;Krishnan H;Pastorino JG;Nevel E;Kephart D;Lee JJ;Retzbach EP;Shen Y;Fatahzadeh M;Baredes S;Kalyoussef E;Honma M;Adelson ME;Kaneko MK;Kato Y;Young MA;Deluca-Rapone L;Shienbaum AJ;Yin K;Jensen LD;Goldberg GS
Podoplanin（PDPN）是一种独特的跨膜受体，可促进肿瘤细胞运动。事实上，PDPN可以作为原发性和转移性癌细胞的化疗靶标，特别是引起大多数口腔癌的口腔鳞状细胞癌（OSCC）细胞。在这里，我们研究了靶向PDPN的单克隆抗体（NZ-1）和凝集素（MASL）如何影响人OSCC细胞的运动性和活力。两种试剂在纳摩尔浓度下抑制PDPN表达OSCC细胞的迁移，然后在微摩尔浓度下抑制细胞活力。此外，这两种试剂诱导线粒体膜通透性转变，通过caspase非依赖性非凋亡性坏死杀死表达PDPN的OSCC细胞。此外，MASL显示出令人惊讶的强大的能力，在暴露的几分钟内靶向PDPN的OSCC细胞，并显着抑制人类OSCC传播斑马鱼胚胎。此外，我们还报道了人口腔鳞癌细胞在小鼠体内形成表达PDPN的肿瘤，并诱导PDPN在浸润性宿主小鼠癌相关成纤维细胞中表达。总之，这些数据表明，抗体和凝集素可用于对抗OSCC和表达PDPN的其他癌症。
Podoplanin (PDPN) is a unique transmembrane receptor that promotes tumor cell motility. Indeed, PDPN may serve as a chemotherapeutic target for primary and metastatic cancer cells, particularly oral squamous cell carcinoma (OSCC) cells that cause most oral cancers. Here, we studied how a monoclonal antibody (NZ-1) and lectin (MASL) that target PDPN affect human OSCC cell motility and viability. Both reagents inhibited the migration of PDPN expressing OSCC cells at nanomolar concentrations before inhibiting cell viability at micromolar concentrations. In addition, both reagents induced mitochondrial membrane permeability transition to kill OSCC cells that express PDPN by caspase independent nonapoptotic necrosis. Furthermore, MASL displayed a surprisingly robust ability to target PDPN on OSCC cells within minutes of exposure, and significantly inhibited human OSCC dissemination in zebrafish embryos. Moreover, we report that human OSCC cells formed tumors that expressed PDPN in mice, and induced PDPN expression in infiltrating host murine cancer associated fibroblasts. Taken together, these data suggest that antibodies and lectins may be utilized to combat OSCC and other cancers that express PDPN.
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DOI：
10.1042/bj20071216
发表时间：
2008-04-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Christou CM;Pearce AC;Watson AA;Mistry AR;Pollitt AY;Fenton-May AE;Johnson LA;Jackson DG;Watson SP;O'Callaghan CA
通讯作者：
O'Callaghan CA
影响因子：
7.3
作者：
Astarita JL;Acton SE;Turley SJ
通讯作者：
Turley SJ
DOI：
10.1002/gcc.20808
发表时间：
2010-11
期刊：
Genes, chromosomes & cancer
影响因子：
--
作者：
Cortez MA;Nicoloso MS;Shimizu M;Rossi S;Gopisetty G;Molina JR;Carlotti C Jr;Tirapelli D;Neder L;Brassesco MS;Scrideli CA;Tone LG;Georgescu MM;Zhang W;Puduvalli V;Calin GA
通讯作者：
Calin GA
影响因子：
6.4
作者：
Chandramohan, Vidyalakshmi;Bao, Xuhui;Kaneko, Mika Kato;Kato, Yukinari;Keir, Stephen T.;Szafranski, Scott E.;Kuan, Chien-Tsun;Pastan, Ira H.;Bigner, Darell D.
通讯作者：
Bigner, Darell D.
影响因子：
3
作者：
Hwang, Young Sun;Park, Kwang-Kyun;Chung, Won-Yoon
通讯作者：
Chung, Won-Yoon