Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Cellular adhesion promotes prostate cancer cells escape from dormancy

ABSTRACT: Dissemination of prostate cancer (PCa) cells to the bone marrow is an early event in the disease process. In some patients, following initial treatment, disseminated tumor cells (DTC) proliferate to form active metastases after a prolonged period of undetectable disease known as tumor dormancy. Identifying mechanisms of PCa dormancy and reactivation remain a challenge due to the lack of in vitro models. Here, we characterized in vitro PCa dormancy-reactivation by inducing three apparently dormant patient-derived xenograft (PDX) lines to proliferate through tumor cell contact with each other and with bone marrow stroma. Proliferating PCa cells demonstrated tumor cell-cell contact and integrin clustering on immunofluorescence. Global gene expression analyses on proliferating cells cultured on bone marrow stroma revealed a downregulation of TGFB2 in all of the three proliferating PCa PDX lines when compared to their non-proliferating counterparts. Furthermore, constitutive activation of myosin light chain kinase (MLCK), a downstream effector of integrin-beta1 and TGF-beta2, in non-proliferating cells resumed cell proliferation. This cell proliferation was associated with an upregulation of CDK6 and a downregulation of E2F4. Taken together, our data provide evidence to support cellular adhesion and downregulation of TGFB2 as a potential mechanism by which PCa cells escape from dormancy. Targeting TGF-beta 2-associated mechanism could provide novel opportunities to prevent lethal PCa metastasis. Custom Agilent-016162 44K whole human genome expression oligonucleotide microarrays were used to profile dormant and proliferating cells isolated from three separate LuCaP xenograft lines grown in co-culture with bone marrow stromal cells isolated from a patient with PCa bone metastases. RNA from 10 cells was amplified prior to hybridization against a common reference pool of prostate tumor cell lines.

ORGANISM(S): Homo sapiens

SUBMITTER: Ilsa Coleman

PROVIDER: E-GEOD-64262 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Cellular Adhesion Promotes Prostate Cancer Cells Escape from Dormancy.

Ruppender Nazanin N Larson Sandy S Lakely Bryce B Kollath Lori L Brown Lisha L Coleman Ilsa I Coleman Roger R Nguyen Holly H Nelson Peter S PS Corey Eva E Snyder Linda A LA Vessella Robert L RL Morrissey Colm C Lam Hung-Ming HM

PloS one 20150619 6

Dissemination of prostate cancer (PCa) cells to the bone marrow is an early event in the disease process. In some patients, disseminated tumor cells (DTC) proliferate to form active metastases after a prolonged period of undetectable disease known as tumor dormancy. Identifying mechanisms of PCa dormancy and reactivation remain a challenge partly due to the lack of in vitro models. Here, we characterized in vitro PCa dormancy-reactivation by inducing cells from three patient-derived xenograft (P ...[more]

PMID: 26090669

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Dataset Information

Cellular adhesion promotes prostate cancer cells escape from dormancy

Publications

Cellular Adhesion Promotes Prostate Cancer Cells Escape from Dormancy.

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