z-logo
Premium
Leukocyte trafficking is not affected by multikinase inhibitors sunitinib or sorafenib in mice
Author(s) -
Laurila Juha P.,
Laukkanen Mikko O.,
Joensuu Heikki,
Salmi Marko,
Jalkanen Sirpa
Publication year - 2016
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30285
Subject(s) - sunitinib , sorafenib , cancer research , extravasation , medicine , angiogenesis , in vivo , pharmacology , cancer , immunology , biology , microbiology and biotechnology , hepatocellular carcinoma
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.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here