Tatematsu Masae, Tsukamoto Tetsuya, Inada Kenichi
Division of Oncological Pathology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa, Nagoya 464-8681.
Cancer Sci. 2003 Feb;94(2):135-41. doi: 10.1111/j.1349-7006.2003.tb01409.x.
All of the different types of stomach epithelial cells are known to be derived from a single progenitor cell in each gland. Similarly, cancers develop from single cells, based on data from clonality analysis in C3H/HeN<-->BALB/c chimeric mice. Using gastric and intestinal epithelial cell markers, intestinal metaplasia (IM) can be divided into two major types: a gastric and intestinal (GI) mixed type, and a solely intestinal (I) type. Ectopic expression of Cdx genes and down-regulation of Sox2 in isolated single GI mixed IM glands suggests abnormal differentiation of stem cells that can produce both gastric (G) and I type cells. Similarly, phenotypic expression of gastric cancer cells of each histological type can be clearly classified into G and I type epithelial cells. The heterogeneity of phenotypic expression of gastric cancer cells in individual cancers is assumed to reflect this intrinsic potential for differentiation in two directions. Gastric cancers at early stages, independent of the histological type, mainly consist of G type cells, and phenotypic shift from G to I type expression is clearly observed with progression. The data thus suggest IM may not be a preneoplastic change in gastric carcinoma, but rather that cells of the I type may appear independently in the gastric mucosa in IM and in gastric cancers. Intestinalization of gastric mucosa and cancer cells may represent a kind of homeotic transformation. Whether disturbance of the regulation of Sox2 and Cdx genes may be of importance to the biological behavior of gastric cancers should therefore be clarified in future studies.
已知每种胃腺中的所有不同类型胃上皮细胞均源自单个祖细胞。同样，根据C3H/HeN<-->BALB/c嵌合小鼠的克隆性分析数据，癌症由单个细胞发展而来。利用胃和肠上皮细胞标志物，肠化生（IM）可分为两种主要类型：胃肠（GI）混合型和单纯肠（I）型。在分离的单个GI混合IM腺中，Cdx基因的异位表达和Sox2的下调表明能够产生胃（G）型和I型细胞的干细胞分化异常。同样，每种组织学类型的胃癌细胞的表型表达可明确分为G型和I型上皮细胞。单个癌症中胃癌细胞表型表达的异质性被认为反映了这种双向分化的内在潜力。早期胃癌，无论组织学类型如何，主要由G型细胞组成，随着病情进展，可明显观察到从G型到I型表达的表型转变。因此，数据表明IM可能不是胃癌的癌前变化，而是I型细胞可能在IM的胃黏膜和胃癌中独立出现。胃黏膜和癌细胞的肠化生可能代表一种同源异型转化。因此，Sox2和Cdx基因调控的紊乱是否对胃癌的生物学行为具有重要意义，有待未来研究阐明。
