Juho Suojanen1, Tuula Salo, Timo Sorsa, Erkki Koivunen. 1. Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Institute of Dentistry, University of Helsinki, FI-00014, Finland. juho.suojanen@helsinki.fi
Abstract
BACKGROUND: Leukocyte immunomodulation has great clinical potential as a therapy of inflammatory conditions and cancer. We have recently developed leukocyte alphaMbeta2 integrin targeting small molecule (IMB-10) capable of inhibiting leukocyte migration and recruitment in vitro and in vivo. MATERIALS AND METHODS: The purpose of this study was to investigate the potential anticancer effects of IMB-10 using U937 histiocytic lymphoma, OCI-AML-3 acute myeloid leukemia and HSC-3 tongue squamous cell carcinoma xenografts in athymic nude mice lacking T-lymphocytes. RESULTS: IMB-10 therapy inhibited the growth of both leukemia and lymphoma xenografts and significantly prolonged the survival of the mice with lymphoma. Interestingly, IMB-10 also reduced host leukocyte infiltration in tumors and affected the invasion potential of squamous cell carcinomas. CONCLUSION: IMB-10 has potential as a therapy for leukocytic malignancies, particularly for lymphomas. Since it also inhibited HSC-3 carcinoma invasion, most likely by blockage of the tumor-infiltrating leukocytes, we suggest that the host inflammation process may affect tumor progression also in a T-cell independent manner.
BACKGROUND: Leukocyte immunomodulation has great clinical potential as a therapy of inflammatory conditions and cancer. We have recently developed leukocyte alphaMbeta2 integrin targeting small molecule (IMB-10) capable of inhibiting leukocyte migration and recruitment in vitro and in vivo. MATERIALS AND METHODS: The purpose of this study was to investigate the potential anticancer effects of IMB-10 using U937 histiocytic lymphoma, OCI-AML-3 acute myeloid leukemia and HSC-3 tongue squamous cell carcinoma xenografts in athymic nude mice lacking T-lymphocytes. RESULTS:IMB-10 therapy inhibited the growth of both leukemia and lymphoma xenografts and significantly prolonged the survival of the mice with lymphoma. Interestingly, IMB-10 also reduced host leukocyte infiltration in tumors and affected the invasion potential of squamous cell carcinomas. CONCLUSION:IMB-10 has potential as a therapy for leukocytic malignancies, particularly for lymphomas. Since it also inhibited HSC-3 carcinoma invasion, most likely by blockage of the tumor-infiltrating leukocytes, we suggest that the host inflammation process may affect tumor progression also in a T-cell independent manner.
Authors: Michael Stefanidakis; Katja Karjalainen; Diana E Jaalouk; Carl G Gahmberg; Susan O'Brien; Renata Pasqualini; Wadih Arap; Erkki Koivunen Journal: Blood Date: 2009-07-27 Impact factor: 22.113
Authors: Tanja-Maria Ranta; Juho Suojanen; Oula Peñate-Medina; Olga Will; Robert J Tower; Claus Glüer; Kalevi Kairemo; Carl G Gahmberg; Erkki Koivunen; Timo Sorsa; Per E J Saris; Justus Reunanen Journal: Mol Diagn Ther Date: 2014-02 Impact factor: 4.074