CELL SURFACE PROTEINS AND CELLULAR ADHESION IN HEPATOCARCINOGENESIS

这个项目的主要目标是分析同型性的变化 化学诱导大鼠进化过程中的细胞间黏附 肝癌的发生和鉴定细胞表面蛋白是 参与了这一过程。细胞间同型胶粘剂的检测 新生Fischer大鼠肝脏来源的14个克隆的特性 上皮细胞系(FNRL)显示，克隆的反应两者不同 通过胰酶处理来解离和再聚集率。增加了 克隆之间的粘连与增加的比例有关 克隆中的非整倍体细胞。亲本细胞系和克隆是 不能在没有或存在2 ng/ml的软琼脂中生长 表皮生长因子(EGF)。大鼠肝癌细胞株H4-II-E显示 在解离成单个细胞后重新聚集的能力可以忽略不计 这些细胞很容易在软琼脂中形成集落。显著升高 检测到两种酸性糖蛋白(105cd和67kd)。 “最粘”克隆时的双向凝胶电泳法 刀豆蛋白A(ConA)结合糖蛋白的(2D-PAGE)图谱 克隆与最少粘附性克隆进行比较。2D-PAGE模式 ConA亲和层析分离质膜糖蛋白的研究 在正常情况下，癌前病变和肿瘤肝脏都显示为定性的 以及样本之间的量变。质的差异 由四种新的多肽组成，分别出现在癌前病变和 对照肝脏，肿瘤肝脏中缺乏的四种多肽，以及五种 与对照相比，肿瘤肝脏中出现新的多肽 肝脏。这些发现支持了这样一种假设，即对正常的 细胞表面成分，尤其是参与细胞间的糖蛋白 或细胞与基质的黏附和沟通，可能是导致某些 癌细胞的生物学行为。

The main objective of this project is to analyze changes in homotypic cell-to-cell adhesion during the evolution of chemically induced rat hepatocarcinogenesis and to identify the cell surface proteins that are involved in this process. Examination of intercellular homotypic adhesive properties of 14 clones derived from a neonatal Fischer rat liver epithelial cell line (FNRL) showed that the clones differ both in response to dissociation by trypsin treatment and reaggregation rates. Increased adhesion among the clones was associated with an increased proportion of aneuploid cells in the clones. The parent cell line and the clones were unable to grow in soft agarose in the absence or presence of 2 ng/ml of epidermal growth factor (EGF). The rat hepatoma cell line H4-II-E showed negligible capacity to reaggregate after dissociation into single cells and these cells readily formed colonies in soft agarose. Markedly elevated amounts of two acidic glycoproteins (105 cd and 67 kd) wre detected in the "most adhesive" clone when the two-dimensional gel electrophoresis (2D-PAGE) pattern of concanavalin A (Con A)-binding glycoproteins in this clone was compared to that of the "least adhesive clone." 2D-PAGE patterns of plasma membrane glycoproteins isolated by Con A affinity chromatography from normal, preneoplastic and neoplastic livers showed both qualitative and quantitative changes among the samples. Qualitative differences consisted of four new polypeptides appearing in preneoplastic liver versus control liver, four polypeptides lacking in neoplastic liver, and five polypeptides appearing new in neoplastic liver compared with control liver. These findings support the hypothesis that modulation of normal cell surface components, especially glycoproteins involved in cell-to-cell or cell-to-matrix adhesion and communication, may be responsible for some of the biological behavior of cancer cells.