AlphaMbeta2 integrin modulator exerts antitumor activity in vivo

Anticancer Res. 2007 Nov-Dec;27(6B):3775-81.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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