Transfection of E-Cadherin CDNA in Human Lung Tumor Cells Reduces Invasive Potential of Tumors

Abstract

Lung cancer is a major health-care problem in industrialized countries. With reference to its therapeutic consequences and major histological variations, it is divided into two subgroups - SCLC (small-cell lung cancer) and NSCLC (non-small-cell lung cancer). As an important factor of cell-cell and cell-substratum interaction, cell adhesion molecules (CAMs) seem to play a key role in tumor-cell migration and invasion that lead to metastases.

We investigated human lung tumor cell lines established from histologically documented neoplastic lesions taken in our operating theater. Immunohistological screening showed differences in E-cadherin expression with no clear predominance of SCLC or NSCLC cell lines. Using an invasion model with Matrigel® Matrix and a migration assay, we could demonstrate a more aggressive behavior pattern in E-cadherin-negative cell lines. We transfected E-cadherin cDNA into a formerly negative cell line showing strong invasive behavior in the initial tests in order to investigate the role of E-cadherin in this process.

In this study, we examined E-cadherin cDNA transfection in human bronchial carcinoma cells. At present, transfection is stable with a follow-up time of one year. We could demonstrate that cell lines were remarkably less invasive after transfection of E-cadherin in the invasion model with Matrigel® Matrix.

These results indicate that the E-cadherin CAM plays an important role in lung tumor invasion and metastasis. Further studies are in progress to confirm these findings and to describe a possible role of this CAM in tumor therapy.

Key words

Bronchial carcinoma - Invasion - Transfection - E-Cadherin - Cell adhesion

References

• 1 Albelda S M. Role of integrins and other cell adhesion molecules in tumor progression and metastasis.  Laboratory investigation. 1993;  68 (1) 4-17
• 2 Takeichi M. Cadherins in cancer: implications for invasion and metastasis.  Curr Opin Cell Biol. 1993;  5 (5) 806-811
• 3 Takeichi M. Cadherin cell adhesion receptors as morphogenetic regulator.  Science. 1991;  251 1451-1455
• 4 El-Bahrawy M A, Pignatelli M. E-cadherin and catenins: molecules with versatile roles in normal and neoplastic epithelial cell biology.  Microsc Res Tech. 1998;  43 (3) 224-232
• 5 Ohene-Abuakwa Y, Pignatelli M. Adhesion molecules in cancer biology.  Adv Exp Med Biol. 2000;  465 115-126
• 6 Wu H, et al. Expression of E-cadherin is associated with squamous differentiation in squamous cell carcinomas.  Anticancer Res. 2000;  20 (3A) 1385-1390
• 7 Rimm D L. Molecular cloning of human E-cadherin suggests an novel subdivision of the cadherin superfamily. Biochemical and biophysical research communications.  Biochem Biophys Res Comm. 1994;  200 (3) 1754-1761
• 8 Hirai Y, et al. Expression and role of E- and P-cadherin adhesion molecules in embryonic histogenesis. 1. Lung epithelial morphogenesis.  Development. 1989;  105 (2) 263-270
• 9 Kasper M, et al. Distribution of E-cadherin and Ep-CAM in the human lung during development and after injury.  Histochem Cell Biol. 1995;  103 (4) 281-286
• 10 Ikeguchi M, et al. Reduced E-cadherin expression and enlargement of cancer nuclei strongly correlate with hematogenic metastasis in colorectal adenocarcinoma (in process citation).  Scand J Gastroenterol (MEDLINE record in process). 2000;  35 (8) 839-846
• 11 Sulzer M A, et al. Reduced E-cadherin expression in associated with increased lymph node metastasis and unfavorable prognosis in non-small cell lung cancer.  Am J Respir Crit Care Med. 1998;  157 (4 Pt 1) 1319-1323
• 12 Ochiai A. Dysfunction of cadherin cell adhesion system in cancer invasion and metastasis.  Can To Kagaku Ryoho. 1999;  26 (4) 565-571
• 13 Hidaka N, et al. Expression of E-cadherin, alpha-catenin, beta-catenin, and gamma-catenin in bronchioloalveolar carcinoma and conventional pulmonary adenocarcinoma: an immunohistochemical study.  Mod Pathol. 1998;  11 (11) 1039-1045
• 14 Smythe W R, et al. Cadherin and catenin expression in normal human bronchial epithelium and non-small cell lung cancer.  Lung Cancer. 1999;  24 (3) 157-168
• 15 Toyoyama H, et al. The reduced expression of e-cadherin, alpha-catenin and gamma-catenin but not beta-catenin in human lung cancer.  Oncol Rep. 1999;  6 (1) 81-85
• 16 Kimura K, et al. Clinical significance of S100A4 and E-cadherin-related adhesion molecules in non-small cell lung cancer.  Int J Oncol. 2000;  16 (6) 1125-1131
• 17 Lim S C, et al. The role of E-cadherin expression in non-small cell lung cancer (in Process Citation).  J Korean Med Sci (MEDLINE record in process). 2000;  15 (5) 501-506
• 18 Herbst R S, et al. Differential expression of E-cadherin and type IV collagenase genes predicts outcome in patients with stage 1 non-small cell lung carcinoma.  Clin Cancer Res. 2000;  6 (3) 790-797
• 19 Hirohashi S. Inactivation of the E-cadherin-mediated cell adhesion system in human cancers.  Am J Pathol. 1998;  153 (2) 333-339
• 20 Vermeulen S, et al. Regulation of the invasion suppressor function of the cadherin/catenin complex.  Pathol Res Pract. 1996;  192 (7) 694-707
• 21 Mareel M, et al. Cadherin/catenin complex: a target for antiinvasive therapy?.  J Cell Biochem. 1996;  61 (4) 524-530