AlphaMbeta2 integrin modulator exerts antitumor activity in vivo.
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.


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.


CONCLUSIONS
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.
Suojanen
Juho
J
Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Institute of Dentistry, University of Helsinki, FI-00014, Finland. juho.suojanen@helsinki.fi
Salo
Tuula
T
Sorsa
Timo
T
Koivunen
Erkki
E
D000208:Acute Disease; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects* / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D013844:Thiazoles / Q000009:adverse effects / Q000494:pharmacology*; D014062:Tongue Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D020298:U937 Cells; D023041:Xenograft Model Antitumor Assays
C509839:IMB 10; D016177:Macrophage-1 Antigen; D013844:Thiazoles; D018093:Gelatinases