Deficiencies in the CD40 and CD154 receptor-ligand system reduce experimental lung metastasis Article

International Collaboration

cited authors

  • Ingersoll, Susan Blaydes, Langer, Florian, Walker, Jamie M., Meyer, Todd, Robson, Theresa, Amaya, Mildred, Desai, Hina, Francis, John L., Amirkhosravi, Ali

funding text

  • This study was funded by the Florida Hospital Gala Endowed Program for Oncologic Research. We thank Robert Banks at the University of Central Florida Animal Facility for his excellent technical help. We thank the Radiation Oncology Department at Florida Hospital for their assistance with this study.

abstract

  • It is established that experimental metastasis requires platelet activity. CD154 expressed on and released from activated platelets induces an inflammatory response in endothelial cells and monocytes, including tissue factor production. CD154 has also been shown to activate platelets in vitro and promote thrombus stability in vivo. These CD154 effects may be mediated, at least in part, by CD40 signaling on platelets and vascular endothelial cells. We have previously demonstrated prolonged bleeding and PFA-100 closure times in mice deficient for Cd154 or its receptor Cd40. In the present study, we hypothesized that Cd40 and Cd154 promote lung tumor formation in experimental metastasis in mice. We created mice doubly deficient in Cd40 and Cd154 (Dbl KO) and found them to be both fertile and viable. Injected tumor cells seeded poorly in mice deficient in Cd40 or Cd154, as well as Dbl KO, compared to wild-type mice. We sought to determine whether blood-borne Cd40 versus endothelial Cd40 contribute differentially to reduced experimental lung metastasis, as observed in Cd40 deficient mice. By bone marrow transplantation, we created mice deficient for Cd40 either in the blood compartment but not in the endothelium, or vice versa. We found that mice deficient in blood compartment Cd40 had fewer lung nodules compared to wild-type mice and mice deficient in endothelial Cd40. Our findings suggest an important contribution of the Cd40-Cd154 pathway to experimental lung metastasis. Furthermore, the data points to a selective role for peripheral blood cell Cd40 in this process.

Publication Date

  • October 1, 2009

webpage

published in

category

start page

  • 829

end page

  • 837

volume

  • 26

issue

  • 7

WoS Citations

  • 4

WoS References

  • 40