人肝细胞癌中整合素α5,β1亚基和纤维连接蛋白mRNAs的表达

目的研究肝细胞癌（ＨＣＣ）中整合素α５、β１亚基和纤维连接蛋白（ＦＮ）ｍＲＮＡｓ表达的生物学意义。方法应用Ｎｏｒｔｈｅｒｎ印迹杂交和核酸原位杂交技术，对１５例ＨＣＣ癌组织、５例癌旁肝硬化和３例正常肝组织中整合素α５、β１亚基和ＦＮｍＲＮＡｓ表达作杂交分析。结果高分化ＨＣＣ癌组织中三种ｍＲＮＡｓ表达水平与癌旁及正常肝组织相近，而低、中分化ＨＣＣ癌组织内明显减少，甚至消失（分别Ｐ＜００１）；整合素α５亚基和ＦＮｍＲＮＡｓ主要见于癌细胞胞浆内；ＨＣＣ伴肝内浸润和／或转移组癌组织内三种ｍＲＮＡｓ水平较无浸润转移组显著下降（Ｐ＜００５）；５例伴肝内转移的ＨＣＣ癌组织中ＦＮｍＲＮＡ呈异质性表达。结论ＨＣＣ中整合素α５、β１和ＦＮ蛋白的表达变化系癌细胞基因转录水平下调的结果，可能与ＨＣＣ细胞分化、浸润和转移相关；异质性ＦＮｍＲＮＡ及其编码的ＦＮ蛋白可能在ＨＣＣ转移中有意义。

Expression of integrin alpha 5, beta 1 subunit and fibronectin mRNAs in human hepatocellular carcinoma

OBJECTIVE: To study the biologic significance of the expression of integrin alpha 5, beta 1 subunit and fibronectin (FN) mRNAs in hepatocellular carcinoma (HCC). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.