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

Content Provider	Springer Nature Link
Author	Ingersoll, Susan Blaydes Langer, Florian Walker, Jamie M. Meyer, Todd Robson, Theresa Amaya, Mildred Desai, Hina Francis, John L. Amirkhosravi, Ali
Copyright Year	2009
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.
Starting Page	829
Ending Page	837
Page Count	9
File Format	PDF
ISSN	02620898
Journal	Clinical & Experimental Metastasis
Volume Number	26
Issue Number	7
e-ISSN	15737276
Language	English
Publisher	Springer Netherlands
Publisher Date	2009-07-30
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	CD154 CD40 Experimental metastasis Surgical Oncology Hematology Oncology Biomedicine general Cancer Research
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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