Abstract
Lymphoblastic cell lines derived by Epstein-Barr virus (EBV) immortalization of normal B lymphocytes can reproducibly inhibit tumor growth in nude mice. This anti-tumor activity is due, in part, to a mediator present in the culture supernatant of EBV-immortalized lymphoblastic cells identified as a fragment of calreticulin encompassing the NH2 terminal domain. Recombinant calreticulin NH2 domain (amino acids 1–180), but not calreticulin P domain (amino acids 181–189), can inhibit endothelial cell proliferation in vitro and angiogenesis in vivo. Calreticulin NH2 domain can bind specifically to the extracellular matrix protein laminin and through this binding can interfere with endothelial cell attachment and spread on laminin-coated surfaces. It can also bind directly to endothelial cell membranes. When inoculated subcutanously into nude mice, recombinant calreticulin NH2 domain prevents the development of subcutaneous tumors and reduces the growth of established tumors of various lineages. The capillary vascular network of tumor tissues from mice treated with calreticulin NH2 domain is reduced compared to controls and scattered tumor cell apoptosis is noted, but tumor histology is otherwise similar. Thus, the NH2 domain of calreticulin is detected in the culture supernatant of lymphoblastoid cells and can exert anti-tumor activities acting as an inhibitor of endothelial cell growth and neovascularization.
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Tosato, G., Yao, L., Pike, S.E. (2003). Calreticulin and Tumor Suppression. In: Eggleton, P., Michalak, M. (eds) Calreticulin. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9258-1_16
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DOI: https://doi.org/10.1007/978-1-4419-9258-1_16
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