The CS1 segment of fibronectin is involved in human OSCC pathogenesis by mediating OSCC cell spreading, migration, and invasion.
The CS1 segment of fibronectin is involved in human OSCC pathogenesis by mediating OSCC cell spreading, migration, and invasion.
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DOI：
10.1186/1471-2407-10-330
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发表时间：
2010-06-25
期刊：
影响因子：
3.8
通讯作者：
Kapila YL
中科院分区：
文献类型：
--
作者：
Kamarajan P;Garcia-Pardo A;D'Silva NJ;Kapila YL
纤连蛋白的可变剪接V区或III型连接段III (IIICS)在早期发育、伤口愈合和肿瘤发生中很重要，然而，其在口腔癌中的作用尚未得到充分研究。因此，我们研究了 CS-1（纤连蛋白 CSIII 区域内的关键位点）在人类口腔鳞状细胞癌 (OSCC) 中的作用。为了确定人类正常和口腔 SCC 组织标本中 CS-1 的表达，进行了免疫组织化学分析。 CS1的表达与临床病理因素相关。为了研究 CS-1 在调节 OSCC 细胞扩散、迁移和侵袭中的作用，在 CS-1 肽或 CS-1 阻断肽存在下测定 OSCC 细胞的扩散和迁移，并使用补充有这些肽的基质胶测定 OSCC 细胞的侵袭。此外，将整合素α4siRNA或粘着斑激酶（FAK）反义寡核苷酸转染到OSCC细胞中，以分别检查整合素α4或FAK在CS1介导的细胞扩散和迁移中的机制作用。与正常组织相比，OSCC 组织中 CS-1 的表达水平显着较高 (p < 0.05)。此外，尽管所有 OSCC 组织样本中均存在高水平的 CS-1 表达，但低级别肿瘤的染色程度比高级别肿瘤的染色更强烈。与正常人原代口腔角质形成细胞相比，OSCC 细胞系还表达更高水平的 CS-1 蛋白。正常组织和OSCC组织和细胞之间的总纤连蛋白表达没有显着差异。在体外测定中加入 CS-1 增强了 OSCC 细胞的扩散、迁移和侵袭，而 CS1 阻断肽则抑制这些过程。抑制整合素α4可显着抑制CS1介导的细胞扩散。此外，这种迁移是由粘着斑激酶 (FAK) 介导的，因为 FAK 抑制显着阻止了 CS1 诱导的细胞迁移。这些数据表明纤连蛋白的 CS-1 位点参与口腔癌发病机制并调节 OSCC 细胞的扩散、迁移和侵袭。
The alternatively spliced V region or type III connecting segment III (IIICS) of fibronectin is important in early development, wound healing, and tumorigenesis, however, its role in oral cancer has not been fully investigated. Thus, we investigated the role of CS-1, a key site within the CSIII region of fibronectin, in human oral squamous cell carcinoma (OSCC). To determine the expression of CS-1 in human normal and oral SCC tissue specimens immunohistochemical analyses were performed. The expression of CS1 was then associated with clinicopathological factors. To investigate the role of CS-1 in regulating OSCC cell spreading, migration and invasion, OSCC cells were assayed for spreading and migration in the presence of a CS-1 peptide or a CS-1 blocking peptide, and for invasion using Matrigel supplemented with these peptides. In addition, integrin α4siRNA or a focal adhesion kinase (FAK) anti-sense oligonucleotide was transfected into OSCC cells to examine the mechanistic role of integrin α4 or FAK in CS1-mediated cell spreading and migration, respectively. CS-1 expression levels were significantly higher in OSCC tissues compared to normal tissues (p < 0.05). Also, although, high levels of CS-1 expression were present in all OSCC tissue samples, low-grade tumors stained more intensely than high grade tumors. OSCC cell lines also expressed higher levels of CS-1 protein compared to normal human primary oral keratinocytes. There was no significant difference in total fibronectin expression between normal and OSCC tissues and cells. Inclusion of CS-1 in the in vitro assays enhanced OSCC cell spreading, migration and invasion, whereas the CS1 blocking peptide inhibited these processes. Suppression of integrin α4 significantly inhibited the CS1-mediated cell spreading. Furthermore, this migration was mediated by focal adhesion kinase (FAK), since FAK suppression significantly blocked the CS1-induced cell migration. These data indicate that the CS-1 site of fibronectin is involved in oral cancer pathogenesis and in regulating OSCC cell spreading, migration and invasion.
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影响因子：
4
作者：
Katoh, K;Mohri, H;Okubo, T
通讯作者：
Okubo, T
DOI：
10.1111/j.1349-7006.1990.tb03338.x
发表时间：
1990-10-01
期刊：
JAPANESE JOURNAL OF CANCER RESEARCH
影响因子：
--
作者：
SAIKI, I;MURATA, J;AZUMA, I
通讯作者：
AZUMA, I
影响因子：
4.8
作者：
Kapila, YL;Niu, JJ;Johnson, PW
通讯作者：
Johnson, PW
影响因子：
7.2
作者：
Kamarajan, Pachiyappan;Kapila, Yvonne L.
通讯作者：
Kapila, Yvonne L.
DOI：
10.1016/s0006-291x(05)80785-5
发表时间：
1992-07-15
影响因子：
3.1
作者：
GARCIAPARDO, A;SANCHEZAPARICIO, P;WAYNER, EA
通讯作者：
WAYNER, EA