Decrease in intercellular adhesion molecule-1 (ICAM-1) and urokinase-type plasminogen activator receptor (uPAR) expression promotes tumor cell spreading in vivo.

AC Donadio PhD, MM Remedi PhD, S Frede PhD, GR Bonacci BSc., GA Chiabrando PhD, MC Pistoresi-Palencia PhD

University of Cordoba, Chemical Sciences School, Cordoba, Argentina E-mail:

AIM: Tumor invasion and tumor cell spreading require a finely tuned regulation of the formation and the lost of adhesive contacts among tumor cells and the extracellular matrix. The development of an effective antitumor immune response to control tumor growth is influenced by the tumor cell itself and/or by the tumor microenvironment. We are interested in the association of the expression of adhesion molecules (ICAM-1, uPAR), MHC and B7 antigens related with tumor spreading. METHODS: We have obtained a tumor cell line (TuE-t) from a rat sarcoma. Tumor masses were presented at day 5-7 after TuE-t cells inoculation into normal rats. Tumors grew until day 15 and then they regressed. Tumor, spleen, liver and lymph node biopsies obtained at days 12 and 20 were used for histological examination. TuE-t cells and cell suspensions from tumor biopsies (ivTuE) were stained by indirect immunocytochemistry and analyzed by flow cytometry. Lymphocyte proliferation assay was performed by co-culture of spleen cells and tumor cells. RESULTS: ICAM-1 and uPAR were highly expressed on TuE-t cells. These molecules were less expressed on ivTuE cells which was related to the simultaneous presence of metastases in liver and spleen. We also observed a positive lymphocyte proliferation associated with the increase of MHC class II and B7 molecules in ivTuE-t cells. CONCLUSIONS: Our data show a decrease in the frequency of ICAM-1 and uPAR expressing tumor cells associated with the presence of metastases. We describe the development of a cellular immune response that could control the tumor progression associated with an increase in the expression of MHC class II IA and B7 antigens during tumor development. The balance between adhesive interactions, proteolytic activity and tumorigenicity may control a tumor invasive phenotype.

KEY WORDS: metastasis, immune response, B7 antigens.

For more information, contact

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Metastasis.