Document Detail


A murine model of bone marrow micrometastasis in breast cancer.
MedLine Citation:
PMID:  12498385     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Bone marrow (BM) is one of the most common sites and often the first clinical indication of metastatic progression of breast cancer. Multivariate analyses have shown that the presence of cytokeratin positive tumor cells in the marrow of women with newly diagnosed stage I, II or III breast cancer is an independent predictor of survival. The objective of this study was to develop an orthotopic model of spontaneous BM metastasis to facilitate studies of this process. A murine mammary adenocarcinoma cell line, Clone 66, was transduced with the neomycin resistance gene (Cl66neo) and injected orthotopically into female Balb/c mice. Polymerase chain reaction (PCR) for the neo gene performed on BM cells harvested from tumor bearing mice demonstrated as few as 10(2) injected tumor cells produced BM micrometastases at 4 weeks postinjection. Small foci of tumor cells were identified in the mammary fatpad (mfp) without gross evidence of primary tumors. Higher doses of tumor cells produced BM micrometastases, detectable by PCR, at one week post-injection. Constructs containing green fluorescent protein (GFP) and the neomycin resistance gene (neo) were also transduced into Clone 66 cells (Cl66-GFPneo) and injected into the mfp. GFP transduced tumor cells were identified in multiple tissues in addition to BM by flow cytometric analysis (FACS) but less 13% of the animals developed gross metastases. This model is a clinically relevant tool for the analysis of organ specificity of metastasis.
Authors:
Barbara O'Kane Murphy; Shantaram Joshi; Anne Kessinger; Elizabeth Reed; J Graham Sharp
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical & experimental metastasis     Volume:  19     ISSN:  0262-0898     ISO Abbreviation:  Clin. Exp. Metastasis     Publication Date:  2002  
Date Detail:
Created Date:  2002-12-24     Completed Date:  2003-01-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8409970     Medline TA:  Clin Exp Metastasis     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  561-9     Citation Subset:  IM    
Affiliation:
Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska 68198-6395, USA. bjmurphy@unmc.edu
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / genetics,  pathology*,  secondary*
Animals
Bone Marrow Neoplasms / pathology*,  secondary*
Breast Neoplasms / genetics,  pathology*
Disease Progression
Female
Flow Cytometry / methods
Green Fluorescent Proteins
Luminescent Proteins / analysis,  genetics,  metabolism
Mice
Mice, Inbred BALB C
Neoplasms, Experimental / secretion
Organ Specificity
Polymerase Chain Reaction / methods
Transduction, Genetic
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Luminescent Proteins; 147336-22-9/Green Fluorescent Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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