Expression of cell cycle regulator cdk2ap1 suppresses tumor cell phenotype by non-cell-autonomous mechanisms.
We evaluated the effect of expressing the cell cycle regulator cdk2ap1 in epithelial or stromal cell compartments to reduce SCC growth in vitro and in vivo. Cell-autonomous and/or non-cell-autonomous expression of cdk2ap1 reduced tumor growth and invasion and altered cell cycle, adhesion, invasion, angiogenesis, and apoptotic gene expression, as assessed by several in vitro phenotype assays, quantitative real-time PCR, and in vivo molecular imaging using a novel three-way xenograft animal model. Our findings suggest that the interactions between cancer cells and fibroblasts that promote abnormal growth can be minimized by expressing cdk2ap1, supporting a novel concept by which tumor/growth suppressor genes can impact tumorigenesis phenotypes from non-cell-autonomous interactions within the tumor microenvironment.
Zolochevska
Olga
O
Department of Comparative Biomedical Sciences, Louisiana State University, Baton Rouge, 70803, United States.
Figueiredo
Marxa L
ML
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D017154:Stromal Cells / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
C096151:CDK2AP1 protein, human; D025521:Tumor Suppressor Proteins