Zhao J, Zhai W, Zhang Y
Department of Pathology, Shanghai Medical University, Shanghai 200032.
Zhonghua Bing Li Xue Za Zhi. 1998 Apr;27(2):94-8.
To study the biologic significance of the expression of integrin alpha 5, beta 1 subunit and fibronectin (FN) mRNAs in hepatocellular carcinoma (HCC).
Integrin alpha 5, beta 1 subunit and FN mRNAs were detected by using Northern blot (alpha-32P-labeled cDNA probes) and in situ hybridization (Dig-labeled cDNA probes) in 15 cases of HCC, 5 cases of paracancerous cirrhotic liver and 3 cases of normal liver tissue.
In well-differentiated HCC, the level of integrin alpha 5, beta 1 or FN mRNA expression was similar to those in normal liver and paracancerous cirrhotic liver tissues, but was markedly decreased, even absent in the poorly- and moderately-differentiated HCC tissues (P < 0.01, respectively). The expression of integrin alpha 5 and FN mRNAs was mainly detected in the cytoplasm of HCC cells. In all the HCC cases tested, the expression of integrin alpha 5, beta 1 and FN mRNAs was lower in 8 cases of HCC with focal invasion and/or intrahepatic metastasis than that in the others without invasion or metastasis(P < 0.05). In addition, the heterogeneous expression of FN mRNA was found in 5 cases of HCC with intrahepatic metastasis.
Combined with the immunohistochemical observation before, it might be deduced that the changes of integrin alpha 5 beta 1 and FN protein expression in HCC tissues are because of changing of the mRNA levels related, which might deeply influence the cell differentiation, tumor invasion and metastasis of HCC. The appearance of the heterogeneous FN mRNA and its encoded FN protein might be associated with the development of HCC metastasis.
研究整合素α5、β1亚基及纤维连接蛋白(FN)mRNA在肝细胞癌(HCC)中的表达及其生物学意义。
采用Northern印迹法(α-32P标记的cDNA探针)和原位杂交法(地高辛标记的cDNA探针)检测15例HCC、5例癌旁肝硬化肝组织及3例正常肝组织中整合素α5、β1亚基及FN mRNA的表达。
高分化HCC组织中整合素α5、β1或FN mRNA表达水平与正常肝组织及癌旁肝硬化肝组织相似,但中低分化HCC组织中其表达明显降低,甚至缺失(P均<0.01)。整合素α5及FN mRNA表达主要位于HCC细胞浆内。在所有检测的HCC病例中,8例有局部侵犯和/或肝内转移的HCC组织中整合素α5、β1及FN mRNA表达低于无侵犯和转移者(P<0.05)。另外,5例有肝内转移的HCC组织中发现FN mRNA表达不均一。
结合以往免疫组化观察结果推测,HCC组织中整合素α5β1及FN蛋白表达的改变可能与其相关mRNA水平变化有关,这可能对HCC细胞分化、肿瘤侵袭和转移产生深刻影响。FN mRNA及其编码的FN蛋白表达不均一现象的出现可能与HCC转移的发生有关。