TY - JOUR
T1 - Absence of caveolin-1 leads to delayed development of chronic lymphocytic leukemia in Eμ-TCL1 mouse model
AU - Shukla, Ashima
AU - Cutucache, Christine E.
AU - Sutton, Garrett L.
AU - Pitner, Michael A.
AU - Rai, Karan
AU - Rai, Siddharth
AU - Opavsky, Rene
AU - Swanson, Patrick C.
AU - Joshi, Shantaram S.
N1 - Funding Information:
We thank the Department of Genetics, Cell Biology and Anatomy for the Pilot Project Grant Support and the University of Nebraska College of Medicine Dean's Research and Development funds.
Publisher Copyright:
© 2016 ISEH - International Society for Experimental Hematology.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the United States. The tissue microenvironment, specifically the lymph nodes, influences the biological and clinical behavior of CLL cells. Gene expression profiling of CLL cells from peripheral blood, bone marrow, and lymph nodes revealed Cav-1 as one of the genes that might be involved in the pathogenesis of CLL. We have previously reported that the knockdown of Cav-1 in primary CLL cells exhibits a significant decrease in cell migration and immune synapse formation. However, the precise role of Cav-1 in CLL initiation and progression in vivo is not known. Therefore, we decreased the expression of Cav-1 in vivo by breeding Eμ-TCL1 with cav-1 knockout mice. We observed a significant decrease in the number of CLL cells and rate of proliferation of CLL cells in spleen, liver, and bone marrow from Eμ-TCL1-Cav1-/+ and Eμ-TCL1-Cav1-/- mice as compared with Eμ-TCL1 mice. In addition, there was a significant increase in survival of Eμ-TCL1-Cav1-/+ and Eμ-TCL1-Cav1-/- compared with Eμ-TCL1 mice. Mechanistically, we observed a decrease in MAPK-Erk signaling measured by p-Erk levels in Eμ-TCL1-Cav1-/+ mice when compared with Eμ-TCL1-Cavwt/wt. Together these results indicate that decreased Cav-1 in Eμ-TCL1 mice significantly delays the onset of CLL and decreases leukemic progression by inhibiting MAPK-Erk signaling, suggesting a role for Cav-1 in the proliferation and progression of CLL.
AB - Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the United States. The tissue microenvironment, specifically the lymph nodes, influences the biological and clinical behavior of CLL cells. Gene expression profiling of CLL cells from peripheral blood, bone marrow, and lymph nodes revealed Cav-1 as one of the genes that might be involved in the pathogenesis of CLL. We have previously reported that the knockdown of Cav-1 in primary CLL cells exhibits a significant decrease in cell migration and immune synapse formation. However, the precise role of Cav-1 in CLL initiation and progression in vivo is not known. Therefore, we decreased the expression of Cav-1 in vivo by breeding Eμ-TCL1 with cav-1 knockout mice. We observed a significant decrease in the number of CLL cells and rate of proliferation of CLL cells in spleen, liver, and bone marrow from Eμ-TCL1-Cav1-/+ and Eμ-TCL1-Cav1-/- mice as compared with Eμ-TCL1 mice. In addition, there was a significant increase in survival of Eμ-TCL1-Cav1-/+ and Eμ-TCL1-Cav1-/- compared with Eμ-TCL1 mice. Mechanistically, we observed a decrease in MAPK-Erk signaling measured by p-Erk levels in Eμ-TCL1-Cav1-/+ mice when compared with Eμ-TCL1-Cavwt/wt. Together these results indicate that decreased Cav-1 in Eμ-TCL1 mice significantly delays the onset of CLL and decreases leukemic progression by inhibiting MAPK-Erk signaling, suggesting a role for Cav-1 in the proliferation and progression of CLL.
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U2 - 10.1016/j.exphem.2015.09.005
DO - 10.1016/j.exphem.2015.09.005
M3 - Article
C2 - 26435347
AN - SCOPUS:84949662070
SN - 0301-472X
VL - 44
SP - 30-37.e1
JO - Experimental Hematology
JF - Experimental Hematology
IS - 1
ER -