Pal Samir Kumar, Nguyen Chi Thi Kim, Morita Kei-Ichi, Miki Yoshio, Kayamori Kou, Yamaguchi Akira, Sakamoto Kei
Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo, Japan.
J Oral Pathol Med. 2016 Nov;45(10):730-739. doi: 10.1111/jop.12430. Epub 2016 Feb 5.
THBS1 (thrombospondin-1) is the extracellular matrix (ECM) protein that affects diverse cellular activities. It constitutes the tumor stroma, but the role of THBS1 in oral squamous cell carcinoma (OSCC) development is unclear. The aim of this study was to clarify the relevance of THBS1 in the pathogenesis of OSCC.
The expression of THBS1 was examined in 44 OSCC by immunohistochemical analysis and in 43 OSCC by cDNA microarray analysis. Cell culture experiments were conducted using human OSCC cell lines HSC3 and HO1N1 and mouse fibroblast ST2 cells to examine the effect of TGFB1 on THBS1 expression, and the effect of THBS1 on cellular behaviors.
THBS1 was specifically induced in the tumor microenvironment of OSCC. THBS1 appeared to be produced mainly by the stromal cells, but also by OSCC cells. TGFB1 stimulated THBS1 expression in ST2, primary fibroblasts, and the OSCC cells. THBS1 promoted migration and invasion of HSC3 and HO1N1 in transwell migration assays. THBS1 stimulated the expression of MMP3 (matrix metalloprotease 3), MMP9, MMP11, and MMP13 in ST2 cells and MMP3, MMP11, and MMP13 in HO1N1 cells. The RGD peptide suppressed the THBS1-stimulated migration and upregulation of MMP11 and MMP13.
THBS1 is a tumor-specific ECM protein that is induced by TGFB1 and promotes migration of cancer cells and stimulates the expression of MMPs partly through the integrin signaling, thereby favoring OSCC invasion.
血小板反应蛋白1（THBS1）是一种影响多种细胞活动的细胞外基质（ECM）蛋白。它构成肿瘤基质，但THBS1在口腔鳞状细胞癌（OSCC）发展中的作用尚不清楚。本研究的目的是阐明THBS1在OSCC发病机制中的相关性。
通过免疫组织化学分析检测44例OSCC中THBS1的表达，并通过cDNA微阵列分析检测43例OSCC中THBS1的表达。使用人OSCC细胞系HSC3和HO1N1以及小鼠成纤维细胞ST2细胞进行细胞培养实验，以检测转化生长因子β1（TGFB1）对THBS1表达的影响以及THBS1对细胞行为的影响。
THBS1在OSCC的肿瘤微环境中特异性诱导表达。THBS1似乎主要由基质细胞产生，但OSCC细胞也能产生。TGFB1刺激ST2细胞、原代成纤维细胞和OSCC细胞中THBS1的表达。在Transwell迁移实验中，THBS1促进HSC3和HO1N1细胞的迁移和侵袭。THBS1刺激ST2细胞中基质金属蛋白酶3（MMP3）、MMP9、MMP11和MMP13的表达以及HO1N1细胞中MMP3、MMP11和MMP13的表达。RGD肽抑制THBS1刺激的迁移以及MMP11和MMP13的上调。
THBS1是一种肿瘤特异性ECM蛋白，由TGFB1诱导产生，促进癌细胞迁移并部分通过整合素信号传导刺激基质金属蛋白酶的表达，从而有利于OSCC的侵袭。
