Abstract
Cancer stem cells (CSCs, or tumor-initiating cells) may be responsible for tumor formation in many types of cancer, including breast cancer. Using high-resolution imaging techniques, we analyzed the relationship between a Wnt-responsive, CSC-enriched population and the tumor vasculature using p53-null mouse mammary tumors transduced with a lentiviral Wnt signaling reporter. Consistent with their localization in the normal mammary gland, Wnt-responsive cells in tumors were enriched in the basal/myoepithelial population and generally located in close proximity to blood vessels. The Wnt-responsive CSCs did not colocalize with the hypoxia-inducible factor 1α-positive cells in these p53-null basal-like tumors. Average vessel diameter and vessel tortuosity were increased in p53-null mouse tumors, as well as in a human tumor xenograft as compared with the normal mammary gland. The combined strategy of monitoring the fluorescently labeled CSCs and vasculature using high-resolution imaging techniques provides a unique opportunity to study the CSC and its surrounding vasculature.
Keywords:
Cancer stem cells; In vivo optical imaging; Microvasculature; Signal transduction; Stem cell microenvironment; p53.
©AlphaMed Press.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adenocarcinoma / blood supply*
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Adenocarcinoma / genetics
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Adenocarcinoma / pathology
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Animals
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Blood Vessels / pathology*
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Cell Hypoxia
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Cell Tracking / methods
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Female
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Genes, Reporter
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Genetic Vectors
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Green Fluorescent Proteins / biosynthesis
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Green Fluorescent Proteins / genetics
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Heterografts
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
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Lentivirus / genetics
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Mammary Neoplasms, Experimental / blood supply*
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Mammary Neoplasms, Experimental / genetics
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Mammary Neoplasms, Experimental / metabolism*
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Mammary Neoplasms, Experimental / pathology
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Mice
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Microscopy, Confocal
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Microscopy, Fluorescence, Multiphoton
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Neoplasm Transplantation
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Neoplastic Stem Cells / metabolism*
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Neoplastic Stem Cells / pathology
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Transduction, Genetic
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Triple Negative Breast Neoplasms / blood supply*
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Triple Negative Breast Neoplasms / genetics
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Triple Negative Breast Neoplasms / metabolism*
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Triple Negative Breast Neoplasms / pathology
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Tumor Suppressor Protein p53 / deficiency*
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Tumor Suppressor Protein p53 / genetics
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Wnt Signaling Pathway* / genetics
Substances
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Hif1a protein, mouse
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Hypoxia-Inducible Factor 1, alpha Subunit
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Tumor Suppressor Protein p53
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enhanced green fluorescent protein
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Green Fluorescent Proteins