血小板衍化生长因子及其受体在人胰腺癌局部浸润转移中作用的实验研究

EXPRESSION OF PLATELET DERIVED GROWTH FACTOR AND PDGF RECEPTORS AND ITS LOCAL INVASIVENESS AND METWASTASIS IN HUMAN PANCREATIC CANCER

观察胰腺组织及其癌变标本中血小板衍化生长因子（ＰＤＧＦ）及其受体（ＰＤＧＦＲ）基因表达的变化关系，以探讨它们在人胰腺癌局部侵袭和转移过程中的作用。用诺真法（Ｎｏｒｔｈｅｒｎ－ｂｌｏｔ）和原位杂交（ｉｎｓｉｔｕｈｙｂｒｉｄｉｚａｔｉｏｎ，ＩＳＨ）方法，采用ｃＤＮＡ探针（ＰＤＧＦＡ、Ｂ，ＰＤＧＦＲα、β）对两株胰腺癌细胞（Ｐａｔｕ８９８８、Ｐａｔｕ８９０２）、１５例胰腺癌手术切除标本和８例正常胰腺组织标本进行杂交检测。胰腺癌组织中，ＰＤＧＦＡ、ＰＤＧＦＢ在ＲＮＡ水平的表达与正常胰腺组织相近；而ＰＤＧＦＲα、ＰＤＧＦＲβ尤其是ＰＤＧＦＲα在ＲＮＡ水平的表达，较正常胰腺组织相对提高。ＰａＴｕ细胞株中，有ＰＤＧＦＡ及其ＰＤＧＦＲβ的表达。ＩＳＨ结果显示：ＰＤＧＦＡ、ＰＤＧＦＢ阳性反应深浅不一，胰腺癌与正常胰腺组织无明显差异。胰腺癌细胞中ＰＤＧＦ和ＰＤＧＦＲ均有表达，而ＰＤＧＦＲβ则比较多地定位于结缔组织中的纤维细胞和内皮细胞。ＰＤＧＦ、ＰＤＧＦＲ可能通过对胰腺癌细胞外基质蛋白降解代谢的调控。

To evaluate the potent role of PDGF and PDGFR in processes leading to metastasis and local invasiveness of human ductal adenocarcinomas of the pancreas. In this study, Northern blot and in situ hybridization have shown platelet derived growth factor(PDGF) and PDGF receptors(PDGFR) gene expression in the pancreas and alterations associated with neoplastic transformation. Two cell lines as well as 15 cases of surgical pancreatic specimens were examined, using cDNA probes to PDGF A and B, PDGF receptor α and β(PDGFRα,β). mRNA transcripts encoding PEGF A chain and PDGF receptor β were present in Patu8988 and Patu8902 human pancreatic cancer cells. In the normal human pancreas PDGFA chain mRNA levels were relatively abundant, whereas PDGFB chain mRNA levels were not detected and PDGFRα and PDGFRβ mRNA transcripts were present at low levels, PDGFA>PDGFRβ> PDGFRα. In the pancreatic cancers, PDGF A chain mRNA transcripts were also abundant, and most samples did not exhibit the PDGFB chain mRNA transcript. In addition, there was a significant increase in the levels of PDGFRα and PDGFRβ in the cancer samples by comparison with the normal pancreas. ISH has shown that transcripts coding for PDGF, PDGF receptors were present in cancer cells, and PDGFRβ was abundant in fibroblasts and endothelial cells within the connective tissues. The results suggest the potent role of PDGF and PDGFR in processes leading to metastasis and local invasiveness of human pancreatic cancer cells.