AlphaMbeta2 integrin modulator exerts antitumor activity in vivo.

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.

• Authors: Juho Suojanen, Tuula Salo, Timo Sorsa, Erkki Koivunen
• Journal: Anticancer research (Anticancer Res) 2007 Nov-Dec Vol. 27 Issue 6B Pg. 3775-81 ISSN: 0250-7005 [Print] Greece
• PMID: 18225532 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• IMB 10
• Macrophage-1 Antigen
• Thiazoles
• Gelatinases

Topics

• Acute Disease
• Animals
• Carcinoma, Squamous Cell (drug therapy, immunology, pathology)
• Cell Growth Processes (drug effects)
• Cell Line, Tumor
• Female
• Gelatinases (metabolism)
• Humans
• Leukemia, Myeloid (drug therapy, immunology, pathology)
• Lymphocytes, Tumor-Infiltrating (drug effects, immunology)
• Macrophage-1 Antigen (immunology, metabolism)
• Mice
• Mice, Nude
• Thiazoles (adverse effects, pharmacology)
• Tongue Neoplasms (drug therapy, immunology, pathology)
• U937 Cells
• Xenograft Model Antitumor Assays