不同组织微环境中人胃癌异种移植瘤侵袭性及基质金属蛋白酶谱表达的差异  

Diversity of invasiveness and matrix metalloproteinases expression profile of human gastric carcinoma xenografted in different tissue environments

作　　者：耿敬姝[1] 宋鸿涛[1] 王吾如[2] 

机构地区：[1]哈尔滨医科大学附属第三医院病理科,150040 [2]哈尔滨医科大学病理学教研室

出　　处：《中华病理学杂志》2004年第1期53-56,共4页Chinese Journal of Pathology

摘　　要：目的　探讨组织微环境对癌细胞侵袭性影响机制中基质金属蛋白酶表达的意义。方法　取人胃腺癌组织移植于裸小鼠皮下 ,成瘤后进行皮下和腹腔内传代接种 ,形态学观察 2处异种移植瘤侵袭性的不同并用免疫组织化学链霉素抗生物素蛋白 过氧化物酶法检测基质金属蛋白酶 (MMP) 2、MMP 7、MMP 9、MMP 13、TM1 MMP、TM2 MMP、TM3 MMP 7种MMPs在瘤组织中的表达。结果　人胃癌裸小鼠皮下异种移植瘤呈膨胀性生长 ,侵袭性不明显 ;除MMP 7外 ,其他 6种MMPs在皮下移植瘤细胞及间质中均无表达。腹腔内移植瘤呈侵袭性生长、纤维间质增多 ,多种MMPs均在侵袭前沿的肿瘤细胞及间质中表达。同一瘤株来源的人胃癌细胞在裸小鼠不同组织环境中所呈现的侵袭性及MMPs表达差异均有显著性。结论　 (1)肿瘤细胞与相邻的间质细胞之间存在相互诱导作用 ,组织环境对肿瘤侵袭表型可有决定性的影响。 (2 )MMPs的表达与肿瘤细胞生长方式及侵袭性有密切联系 ;Objective To study the effect of tissue environment on the invasiveness of carcinoma cells and the implication of expression of matrix metalloproteinases. Methods Tissue from a human gastric carcinoma was transplanted and passaged subcutaneously in nude mice. After the 3rd passage, the xenografts were also transplanted into the abdominal cavity of nude mice. The invasiveness of xenografts at the two locations were observed morphologically and the expressions of MMP-2, MMP-7, MMP-9, MMP-13, TM1-MMP, TM2-MMP and TM3-MMP were monit ored by immunohistochemistry. ResultsThe subcutaneous xenografts of human gastric carcinoma in nude mice presented as expanding outgrowths with limited invasion. Except for MMP-7, the other 6 MMPs (MMP-2, MMP-9, MMP-13, TM1-MMP, TM2-MMP, TM3-MMP) were not expressed in the neoplastic cells nor in the tumor stroma. In contrast, the intra-peritoneal xenografts displayed an invasive growth pattern accompanied by more fibrous stroma. All MMPs examined were expressed in the tumor cells at the invasive fronts and in the adjacent stroma. ConclusionsInvasiveness and expression of MMPs were obviously diverse in human gastric carcinoma cells when grafted at different anatomic locations in nude mice, thus indicating: (1)There exists a close interaction between tumor cells and surrounding stromal cells. The tissue environment may play a definitive role in the tumor phenotype. (2) The expression of MMPs is closely related to the growth pattern and the invasiveness of tumor cells. MMPs produced by the stroma cells at the invasion front may be linked to the invasiveness of neoplastic cells.

关 键 词：胃癌 异种移植瘤 肿瘤侵袭性 基质金属蛋白酶 癌细胞 细胞外基质 

分 类 号：R735.2[医药卫生—肿瘤]