Overexpression of L1CAM in non-small cell lung cancer: Clinical implications and molecular characterization. Free

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L1CAM (L1) is a 200kD type I transmembrane protein of immunoglobulin superfamily, which is known to play an important role in development of nervous system. On the other hand, recently it has reported that L1 may be associated with poor prognosis of ovarial and uterine cancer (Lancet 2003, Fogel et al). The L1 ectodomain is cleaved by the metalloproteinase ADAM 10 in human tumor cell lines. The biological role for L1 in various cancers remains to be controversial. To investgate L1 involved in progression of nonsmall cell lung cancer, we performed an immunohistochemical study using anti- L1 antibody and L1 mRNA by RT-PCR analysis. In addition, we evaluated ADAM 10 expression using the same samples. We also clarify the mechanism of L1 expression and effect of L1 on cell migration using lung cancer cell lines. <.Method> We used surgical resected samples of non small cell lung cancer (50 cases: adeno.41, sq. 9, I:21, II :5, III :24). Using paraffin embedded section, immunohistochemical studies for L1 and ADAM 10 were carried out by LSAB method. L1 and ADAM 10 mRNA in non-cancerous and cancerous tissue was analyzed by RT-PCR. The analysis of ankyrin and F-actin using lung cancer cell lines(PC 9,A 549, PC 14, LCA-1) was carried out. Invasion assay after L1 siRNA treatment was examined. Bronchial glands were weak positive in normal lung tissue. A part of adencarcinoma.and squamous cell carcinoma showed strong positive in cytoplasm. Positive rate was 79.1%(19/24) for stageIII group, 20%(1/5) for stage II group and 57.1% (12/21) for stageIgroup(p=0.03, I + II vs III). Four-year survival rates after operation were 43.9% for L1 -positive group and 91.7% for L1-negative group (p=0.017). L1 and ADAM 10 mRNA could be detected higher in cancerous tissues than in non-cancerous tissues. Co-expression of ankyrin, F-actin and L1 could be observed in lung cancer cell lines.According to invasion assay after L1 siRNA treatment, decreased effect of tumor cell migration was shown. These results suggest that L1 in nonsmall cell lung cancer expresses related to ADAM10,and overexpression of L1 may predict poor prognosis. Additionally, L1 played a role in enhanced tumor cell migration