Molecular characterization of disseminated tumor cells from colorectal cancer: nuclear beta-catenin defines subpopulation with higher chromosomal instability (CIN)
2009; Springer Nature; Linguagem: Inglês
10.1007/978-3-642-00625-8_25
ISSN1432-9336
AutoresM. Nübel, S. Kraus, Alexander Rehders, Feride Aydin, Stefan A. Topp, Claus Ferdinand Eisenberger, Stephan Baldus, Wolfram Trudo Knoefel, N. H. Stoeklein,
Tópico(s)Cancer-related gene regulation
ResumoThe Wnt-pathway, with nuclear beta-catenin as a main effector protein, can induce Epithelial-Mesenchymal Transition (EMT) and indirectly chromosomal instability (CIN). Here, we investigated for disseminated tumor cells (DTC) expressing nuclear beta-catenin and if this phenotype is associated with specific genomic alterations. Therefore, we established a double-immunfluorescence labelling protocol to determine the staining pattern of beta-catenin in single disseminated tumor cells. Single CK-positive cells were isolated by micromanipulation, their DNA was globally amplified by an adapter-linker PCR method and their genomes were subsequently screened for chromosomal gains and losses using comparative genomic hybridization (CGH). We detected 34 CK-positive cells in 20 bone marrow samples of 68 CRC patients (29%). CGH analysis revealed a higher mean chromosomal aberration number (11,4) for cells expressing beta-catenin in the nucleus compared to those with cytoplasmatic or absent beta-catenin staining (4,1). Our results demonstrated a variable expression of beta-catenin on early DTCs detected in bone marrow of CRC patients. However, a significant number showed nuclear beta-catenin staining, indicating activated Wnt signaling. Interestingly, cells with nuclear beta-catenin displayed the highest level of chromosomal instability. Ongoing research will clarify, whether these cells confer a higher risk for metastatic relapse.
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