Analysis of the function of TM4SF complex and lung cancer gene therapy based on using this complex.

各期细胞系的建立对阐明TM4SF复合体的异常起着至关重要的作用。以前，我们报道过在这种胶原中混合50%的基质蛋白是建立细胞系的最有效的方法。在上述混合物中加入10%的患者血清可以更容易地建立细胞系。利用该方法，建立了三种AAH模型。MRP-1/CD9、KAI1/CD82在这些细胞系中无异常表达。PETA3/CD15I表达也呈下降趋势。在此基础上，建立了10个I期肺癌细胞系和9个II期肺癌细胞系。我们尝试建立了13个术前化疗的III期肺癌细胞系，但由于大部分部位是坏死区，所以只建立了4个细胞系。从转移灶标本中建立了6种IV期细胞系。然后，分析了mrp1/CD9PETA3/CD151、、KAI1/CD82的复合体形成。在I期，除1株外，其余2株细胞均有MRP-1/CD9和KAI1/CD82的表达，而PETA3/CDI5I表达较弱。Ⅱ期5例KAI1/CD82降低，1例MRP-1/CD9降低，2例PETA3/CD151升高。III期仅4例KAII/CD82下降。后1例仅表达PETA3/CD151。在第IV期，几乎所有转移细胞系的、表达均为阳性。从这些实验来看，MRP-1/CD9和KAI1/CD82作为肿瘤转移抑制基因发挥了重要作用。另一方面，PETA3/CD151起着促进肿瘤转移的作用。因此，这些表达的平衡和失衡与肿瘤的转移过程有关。

Establishment of cell lines in each stage plays a most important role to clarify abnormality of the TM4SF complex. Previously, we reported mixing 50% matrigel in this collagen is the most efficient for establishment of the cell lines. Adding 10% of patients' serum in the above mixture made it easier to establish the cell line. Using this method, three kinds of AAH were established. There were no abnormality in the expression of MRP-1/CD9、KAI1/CD82 in these cell lines. And also PETA3/CD15I expression appeared decreasing. Next, 10 cell lines were established in Stage I lung cancer, 9 cell lines were established in Stage II lung cancer. We tried to establish 13 cell lines in Stage III lung cancer that did chemotherapy before the operation, however only 4 cell lines were established because most of the parts were necrotic region. Six kinds of cell lines in StageIV were established from the specimens of metastasis region. Then, the complex formation of MRP-1/CD9、KAI1/CD82 and PETA3/CD 151 were analyzed. In the Stage I, MRP-1/CD9 and KAI1/CD82 expression were found in two cell lines except one, but PETA3/CDI5I appeared weak expression. In the Stage II, KAI1/CD82 was decreasing in 5 cases and MRP-1/CD9 was decreasing in I. case, however PETA3/CD151 was increasing in 2 cases. In the StageIII, only KAII/CD82was found decreasing in 4 cases. Then only PETA3/CD151 was appeared in the last 1case. In the StageIV、 expression of PETA3/CD151 was positive in almost all metastatic cell lines. From these experiments, MRP-1/CD9 and KAI1/CD82 play an important role as metastasis suppressor genes. On the other hand, PETA3/CD151 plays a metastasis promotion gene. Hence, the balance and unbalance of these expressions have something to do with the process of metastasis.