Experimental Study of the Established Cell Line Derived from Human Mucoepidermoid Carcinoma of the Metastatic Submandibular Lymph Nodes

Mucoepidermoid carcinoma (MEC) has been thought to be common malignant tumors of salivary gland. The biological characteristics, however, has been unclear especially in growth, fibrinolytic and angiogenic activity. Therefore, I established a new cell line (designated IT-2) derived from the metastatic submandibular lymph nodes of a patient with mucoepidermoid carcinoma arising in the mandibular alveolus. The biological characteristics of IT-2 were examined by the following methods ; 1) morphological study, 2) chromosomal analysis, 3) growth curve, 4) DNA synthetic activity affected by some growth factors or their antibodies, 5) angiogenic activity by measuring 3 H-thymidine incorporation of bovine capillary endothelial cells cultured by conditioned medium (CM) with or without neutralizing antibodies against angiogenic factors, 6) fibrinolytic activity by examination of mRNA expression for tissue type and urokinase type plasminogen activator (tPA and uPA) by Northern blot analysis, 7) checkerboard analysis of IT-2 cells migration induced by conditioned medium of human fibroblast cells (hFib-CM), 8) invasive activity into Type I collagen gel and basement menbrane (matrigel) induced by hFib-CM with or without neutralizing basic fibroblast growth factor antibody, 9) collagenolytic activity on gelatin zymography. Growth activity of IT-2 cells seemed to be dependent on epidermal growth factor and platelet derived growth factor-A chain. Angiogenic activity of CM was related to either basic fibroblast growth factor or vascular endothelial growth factor. While mRNA expression of uPA was detected, mRNA of tPA was not. Invasive and migrating activities were enhanced by hFib-CM. IT-2 cells produced matrix metalloproteinase 2 and 9. IT-2 cells seem to be the useful cell line for examination of biology of MEC.