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Monoclonal growth during chimeric mouse carcinogenesis demonstrated by a strain-specific antibody and microsatellite DNA polymorphism patterns.

通过品系特异性抗体和微卫星 DNA 多态性模式证明嵌合小鼠致癌过程中的单克隆生长。

基本信息

批准号：
06670250
负责人：
TATEMATSU Masae
金额：
$ 1.34万
依托单位：
AICHI CANCER CENTER
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

The clonality of epithelial proliferative lesions associated with colon and forestomach carcinogenesis was immunohistochemically investigated in C3H/HeN**BALB/c chimeric mice using a specific antibody to C3H strain specific antigen (CSA) and as well as in terms of microsatellite DNA polymorphism patterns. In normal colonic mucosa of the chimeras, each gland was composed entirely of either CSA positive or negative cells and no mixed glands were found. Cells of all focal atypias in chimeric mice were, in each case, homogeneous for one or other of the parental types. Of 91 adenomas in chimeric mice, only one comprised both types of cells. Among 119 adenocarcinomas, 12 contained cells of both parental types. Normal chimeric forestomach epithelium was found to demonstrate mixtures of epithelial cell groups composed of either CSA positive or negative cells. The same was the case for all simple hyperplasias. Many PN-hyperplasias, in contrast, consisted of both CSA positive and negative cell groups. Squamous cell carcinomas were composed entirely of either CSA positive or negative tumor cells. However in animals with multiple advanced CSA positive cancers and negative cancers, cancer nests composed of both parental type cells were found in association. Microsatellite DNA ploymorphism patterns sampled from histological sections completely conformed with the outcome of immunohistochemical staining. The results suggest that individual cancers are derived from single cells showing monoclonal growth, with apparently polyclonal tumors arising secondarily during progression, due to two or more lesions coalescing.

用抗C3 H株特异性抗原（CSA）的特异性抗体和微卫星DNA多态性模式，对C3 H/HeN**BALB/c嵌合小鼠结肠癌和前胃癌发生相关的上皮增生性病变的克隆性进行了免疫组化研究。在正常的结肠粘膜的嵌合体，每个腺体完全由CSA阳性或阴性细胞和没有混合腺体被发现。细胞的所有局灶性结肠炎的嵌合体小鼠，在每种情况下，同质的一个或其他的父母类型。在嵌合体小鼠的91个腺瘤中，只有一个包含两种类型的细胞。在119例腺癌中，12例包含两种亲本类型的细胞。正常嵌合前胃上皮细胞被发现证明由CSA阳性或阴性细胞组成的上皮细胞群的混合物。所有单纯性增生也是如此。相反，许多PN增生由CSA阳性和阴性细胞群组成。鳞状细胞癌完全由CSA阳性或阴性肿瘤细胞组成。然而，在患有多种晚期CSA阳性癌症和阴性癌症的动物中，发现由两种亲本类型细胞组成的癌巢是相关的。组织切片中的微卫星DNA多态性与免疫组化结果完全一致。结果表明，个别癌症是来自单克隆生长的单细胞，由于两个或多个病变合并，在进展过程中出现明显的多克隆肿瘤。