SIKVAV, a laminin α1-derived peptide, interacts with:: Integrins and increases protease activity of a human salivary gland adenoid cystic carcinoma cell, line through the ERK 1/2 signaling pathway
SIKVAV, a laminin α1-derived peptide, interacts with:: Integrins and increases protease activity of a human salivary gland adenoid cystic carcinoma cell, line through the ERK 1/2 signaling pathway
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DOI：
10.2353/ajpath.2007.051264
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发表时间：
2007-07-01
影响因子：
6
通讯作者：
Jaeger, Ruy G.
中科院分区：
文献类型：
--
作者：
Freitas, Vanessa M.;Vilas-Boas, Vanessa F.;Jaeger, Ruy G.
腺样囊性癌是一种常见的涎腺恶性肿瘤。我们研究了诱导蛋白酶活性的层粘连蛋白衍生肽，SIKVAV，在细胞（CAC 2）来自这种肿瘤。层粘连蛋白α 1和基质金属蛋白酶（MMPs）2和9在腺样囊性癌细胞在体内和体外的免疫定位。SIKVAV上培养的CAC 2细胞显示MMP 9的剂量依赖性增加，如通过酶谱和α 3和α 6整合素的共定位所检测到的。小干扰RNA（siRNA）敲低整合素在CAC 2细胞中的表达导致与肽的粘附减少。SIKVAV亲和层析和免疫印迹分析显示，α 3、α 6和β 1整联蛋白从SIKVAV柱洗脱，这通过质谱和固相结合测定证实。小干扰RNA实验还表明，这些整合素，通过细胞外信号调节激酶（ERK）1/2信号，调节MMP分泌SIKVAV诱导的CAC 2细胞。我们认为SIKVAV通过α 3 β B和α 6 β 1整合素以及ERK 1/2信号通路增加人涎腺腺样囊性癌细胞系的蛋白酶活性。
Adenoid cystic carcinoma is a frequently occurring malignant salivary gland neoplasm. We studied the induction of protease activity by the laminin-derived peptide, SIKVAV, in cells (CAC2) derived from this neoplasm. Laminin alpha 1 and matrix metalloproteinases (MMPs) 2 and 9 were immunolocalized in adenoid cystic carcinoma cells in vivo and in vitro. CAC2 cells cultured on SIKVAV showed a dose-dependent increase of MMP9 as detected by zymography and colocalization of alpha 3 and alpha 6 integrins. Small interfering RNA (siRNA) knockdown of integrin expression in CAC2 cells resulted in decreased adhesion to the peptide. SIKVAV affinity chromatography and immunoblot analysis showed that alpha 3, alpha 6, and beta 1 integrins; were eluted from the SIKVAV column, which was confirmed by mass spectrometry and a solid-phase binding, assay. Small interfering RNA experiments also showed that these integrins, through extracellular signal-regulated kinase (ERK) 1/2 signaling, regulate MMP secretion induced by SIKVAV in CAC2 cells. We propose that SIKVAV increases protease activity of a human salivary gland adenoid cystic carcinoma cell line through alpha 3 beta b and alpha 6 beta 1 integrins and the ERK 1/2 signaling pathway.