恶性肿瘤体内外生长和发展过程与细胞外基质相关性的研究

Relationship between extracellular matrix and progressive growth of malignant tumor

目的探讨细胞外基质在肿瘤侵袭转移中的作用。方法利用小鼠肺腺癌细胞母系ＬＡ７９５移植于Ｔ７３９小鼠皮下和肾包膜下，以及人鼻咽癌细胞系ＣＮＥ－２Ｚ移植于裸小鼠皮下等体内移植模型，通过间接免疫酶标和间接免疫荧光技术，测定纤维粘连蛋白（ＦＮ）、层粘连蛋白（ＬＮ）与Ⅳ型胶原（ⅣＣ）在肿瘤移植后不同时间的表达，并利用多种体外实验方法（琼脂糖滴瘤细胞移动实验、软琼脂上瘤细胞集落生长速度测定、斑点杂交等），分析瘤细胞运动能力、瘤细胞集落生长速度等与ＬＮ、ＦＮ和ⅣＣ之间的关系。结果随着肿瘤的生长，ＦＮ、ＬＮ与ⅣＣ的表达均增强，且呈不同的分布；外源性ＦＮ、ＬＮ及ⅣＣ能提高瘤细胞的体外运动能力和促进瘤细胞集落的体外生长。结论细胞外基质的分布及其合成和降解的变化，与恶性肿瘤的侵袭和转移有关，对预测肿瘤生物学行为有参考价值。观察细胞外基质与瘤细胞侵袭的关系。

Objective To explore the role of extracellular matrix proteins in tumor cell invasion and metastasis. Methods Mouse pulmonary adenocarcinoma cell line LA 795 and human nasopharyngeal carcinoma cell line CNE 2Z were implanted subcutaneously and under the renal capsule in T 739 and nude mice, respectively. At different time intervals, expression of fibronectin(FN), laminin(LN) and type Ⅳ collagen(Ⅳ C) in the tumor extracellular matrix and in tumor adjacent tissues was examined by indirect immunoperoxidase and immunofluorescence techniques. In addition, various in vitro methods ( random migration of tumor cells in agarose droplet, growth of tumor cell colonies in soft agar, dot blotting, etc.) were used to analyse the effect of exogenous LN, FN or ⅣC. Results As tumor grew, the expression of FN, LN or ⅣC increased and presented different distribution patterns. Exogenous FN, LN and Ⅳ C enhanced the mobility of tumor cells and the growth of the tumor cell colonies. Conclusion The distribution difference and the changes in synthesis and degradation of the extracellular matrix proteins are valuable in predicting the biologic behaviour. Tumor implanted under the renal capsule of mice offers a better experimental model to study the relationship between extracellular matrix and tumor cell invasion.