Leukocyte trafficking is not affected by multikinase inhibitors sunitinib or sorafenib in mice

Juha P. Laurila, Mikko O. Laukkanen, Heikki Joensuu, Marko Salmi, Sirpa Jalkanen

Research output: Contribution to journalArticlepeer-review

Abstract

Sunitinib and sorafenib are broad-spectrum tyrosine kinase inhibitors (TKI) targeting, for example, VEGF1-3, PDGFRb, RET, FLT3, CD117 (c-KIT) and CSF-1R cell membrane receptors thus suppressing tumor angiogenesis and cancer cell growth. Recently it has been suggested that the kinases targeted by Sunitinib and/or Sorafenib regulate leukocyte transmigration, which might in part be responsible for the often-observed reduction in tumor-associated myeloid derived suppressor cells and regulatory T cells. The aim of the current study is to determine whether sunitinib or sorafenib inhibit leukocyte extravasation. Sunitinib, sorafenib, or vehicle treated animals did not show any difference in leukocyte trafficking either in peritonitis or in vivo homing experiments, although sunitinib treatment effectively inhibited growth of B16 melanoma tumors in WT, SCID and SCID beige mice. Inhibition of tumor growth was associated with an increased number of infiltrating CD11b+ cells in the tumor, while the numbers of CD8, Gr-1 and F4/80 expressing cells were unchanged. In conclusion, the findings suggest that despite multiple targets with a potential role in leukocyte extravasation, neither sunitinib nor sorafenib effectively inhibits this process in vivo. Thus, the observed specific effect on CD11b cells among tumor infiltrating leukocytes is most likely an indirect effect.

Original languageEnglish
Pages (from-to)2270-2276
Number of pages7
JournalInternational Journal of Cancer
Volume139
Issue number10
DOIs
Publication statusPublished - Nov 15 2016

Keywords

  • leukocyte traffic
  • migration
  • multikinase inhibitors

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

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