Cellular Adhesion Promotes Prostate Cancer Cells Escape from Dormancy.

摘要: Dissemination of prostate cancer (PCa) cells to the bone marrow is an early event in disease process. In some patients, disseminated tumor (DTC) proliferate form active metastases after a prolonged period undetectable known as dormancy. Identifying mechanisms PCa dormancy and reactivation remain challenge partly due lack vitro models. Here, we characterized dormancy-reactivation by inducing from three patient-derived xenograft (PDX) lines through cell contact with each other stroma. Proliferating demonstrated cell-cell integrin clustering immunofluorescence. Global gene expression analyses on proliferating cultured stroma revealed downregulation TGFB2 all PDX when compared their non-proliferating counterparts. Furthermore, constitutive activation myosin light chain kinase (MLCK), downstream effector integrin-beta1 TGF-beta2, promoted proliferation. This proliferation was associated upregulation CDK6 E2F4. Taken together, our data provide first clinically relevant model support cellular adhesion potential mechanism which may escape Targeting TGF-beta2-associated could novel opportunities prevent lethal metastasis.