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A new anti-cancer strategy by control ling crosstalk of oral carcinoma cells with extracellular matrix molecules

控制口腔癌细胞与细胞外基质分子串扰的抗癌新策略

基本信息

批准号：
14370581
负责人：
SAKU Takashi
金额：
$ 9.6万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

It was poorly understood which cell types, tumor cells or stromal cells, were responsible for the production of extracellular matrix (ECM) molecules in the neoplastic stroma. To investigate the role of each cell type's participation in the production of ECM molecules, as a primary experiment of this research project, the expression of four ECM molecules at the protein and the mRNA levels was studied in two kinds of co-culture systems in direct and indirect contacts between squamous cell carcinoma (SCC) cell systems and stromal fibroblast cell systems. While similar protein and mRNA expression levels for perlecan and other ECM molecules between SCC cells and fibroblasts in a monocellular culture condition, these ECM expression levels of fibroblasts were elevated, and instead those of SCC cells dropped when they were in contact with SCC cells. The differences in the levels between SCC cells and fibroblasts were significantly more evident in direct contact than in indirect contact. These results indicated that oral SCC cells produce ECM molecules in the absence of stromal fibroblasts, which correspond to carcinomas in-situ, and that they stop producing ECM in the presence of fibroblasts, which correspond to invasive SCC. These phenomena were also confirmed in tissue sections from oral carcinoma surgical specimens by immunohistochemistry and in-situ hybridization. In other experiments, ECM production and its metabolism were shown to be controlled by both parenchymal and stromal cells. It is thus suggested that stromal fibroblasts after direct contact with invading SCC cells are more responsible than SCC cells for the formation of neoplastic stroma, and that histological invasion of SCC can be defined as the presence of stromal induction. Based on the findings, we have proposed a tumor biological concept of "parenchymal-stromal switching for ECM production."

在肿瘤间质中，究竟是肿瘤细胞还是基质细胞负责细胞外基质（ECM）分子的产生，目前尚不清楚。为了研究每种细胞类型参与ECM分子产生的作用，作为本研究项目的主要实验，研究了在鳞状细胞癌（SCC）细胞系统和间质成纤维细胞系统直接和间接接触的两种共培养系统中，四种ECM分子在蛋白质和mRNA水平上的表达。虽然在单细胞培养条件下，SCC细胞和成纤维细胞之间的perlecan和其他ECM分子的蛋白质和mRNA表达水平相似，但当成纤维细胞与SCC细胞接触时，这些ECM表达水平升高，而SCC细胞的ECM表达水平则下降。SCC细胞和成纤维细胞之间的水平差异在直接接触时比间接接触时更为明显。这些结果表明，口腔SCC细胞在没有基质成纤维细胞（对应于原位癌）的情况下产生ECM分子，并且在存在成纤维细胞（对应于侵袭性SCC）的情况下停止产生ECM。这些现象在口腔癌手术标本的组织切片上也得到了免疫组织化学和原位杂交的证实。在其他实验中，ECM的产生及其代谢被证明是由实质细胞和基质细胞共同控制的。因此，我们认为，与侵袭的鳞状细胞直接接触后的间质成纤维细胞比鳞状细胞更容易形成肿瘤间质，鳞状细胞的组织学侵袭可以定义为基质诱导的存在。基于这些发现，我们提出了一个肿瘤生物学概念，即“实质-间质转换导致ECM的产生”。

项目成果

期刊论文数量（64）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Perlecan, a basement membrane type heparan sulfate proteoglycan, in the epithelial space : a possibility is a new concept of intraepithelial stroma.

Perlecan，一种基底膜型硫酸乙酰肝素蛋白多糖，位于上皮间隙：一种可能性是上皮内基质的新概念。

DOI：
发表时间：
2004
期刊：
Niigata Dental Journal 34(2)
影响因子：
0
作者：
Ida H;Saku T
通讯作者：
Saku T

Extracellular matrix remodeling in oral submucous fibrosis:: its stage-specific modes revealed by immunohistochemistry and in situ hybridization

DOI：
10.1111/j.1600-0714.2005.00339.x
发表时间：
2005-09-01
期刊：
JOURNAL OF ORAL PATHOLOGY & MEDICINE
影响因子：
3.3
作者：
Utsunomiya, H;Tilakaratne, WM;Saku, T
通讯作者：
Saku, T

Nucleotide sequences and functions of the Epstein-Barr virus latent membrane protein 1 genes isolated from salivary gland lymphoepithelial carcinomas

从唾液腺淋巴上皮癌中分离出的 Epstein-Barr 病毒潜伏膜蛋白 1 基因的核苷酸序列和功能

DOI：
发表时间：
2005
期刊：
Virus Genes 30(2)
影响因子：
0
作者：
Masahiro Morita;Toru Suzuki;Kentaro Ito;Tadashi Yamamoto;Hall WW;Niinuma A;Tsubata C;Higuchi M;Kawakami H;Jen KY
通讯作者：
Jen KY

Ida-Yonemochi H: "The basement membrane type heparan sulfate proteoglycan (perlecan) in ameloblastomas : its intercellular localization in stellate reticulum-like foci and biosynthesis by tumor cells"Virchows Arch. 441(2). 165-173 (2002)

Ida-Yonemochi H：“成釉细胞瘤中的基底膜型硫酸乙酰肝素蛋白多糖（基底膜聚糖）：其在星状网状病灶中的细胞间定位以及肿瘤细胞的生物合成”Virchows Arch。