title: Wnt-responsive cancer stem cells are located close to distorted blood vessels and not in hypoxic regions in a p53-null mouse model of human breast cancer.
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.
authors.affiliation: Department of Molecular Physiology and Biophysics, Lester & Sue Smith Breast Center, Departments of Molecular and Cellular Biology and Radiology, and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA; Department of Systems Medicine and Bioengineering, The Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, Texas, USA; Department of Developmental Biology, Pittsburgh, Pennsylvania, USA; Women's Cancer Research Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA vadakkan@bcm.edu meizhang@pitt.edu.
authors.forename: Tegy J
authors.initials: TJ
authors.lastname: Vadakkan
authors.affiliation: Department of Molecular Physiology and Biophysics, Lester & Sue Smith Breast Center, Departments of Molecular and Cellular Biology and Radiology, and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA; Department of Systems Medicine and Bioengineering, The Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, Texas, USA; Department of Developmental Biology, Pittsburgh, Pennsylvania, USA; Women's Cancer Research Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Landua
authors.affiliation: Department of Molecular Physiology and Biophysics, Lester & Sue Smith Breast Center, Departments of Molecular and Cellular Biology and Radiology, and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA; Department of Systems Medicine and Bioengineering, The Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, Texas, USA; Department of Developmental Biology, Pittsburgh, Pennsylvania, USA; Women's Cancer Research Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Bu
authors.affiliation: Department of Molecular Physiology and Biophysics, Lester & Sue Smith Breast Center, Departments of Molecular and Cellular Biology and Radiology, and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA; Department of Systems Medicine and Bioengineering, The Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, Texas, USA; Department of Developmental Biology, Pittsburgh, Pennsylvania, USA; Women's Cancer Research Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Molecular Physiology and Biophysics, Lester & Sue Smith Breast Center, Departments of Molecular and Cellular Biology and Radiology, and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA; Department of Systems Medicine and Bioengineering, The Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, Texas, USA; Department of Developmental Biology, Pittsburgh, Pennsylvania, USA; Women's Cancer Research Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
authors.forename: Fuhai
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Molecular Physiology and Biophysics, Lester & Sue Smith Breast Center, Departments of Molecular and Cellular Biology and Radiology, and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA; Department of Systems Medicine and Bioengineering, The Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, Texas, USA; Department of Developmental Biology, Pittsburgh, Pennsylvania, USA; Women's Cancer Research Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
authors.forename: Stephen T C
authors.initials: ST
authors.lastname: Wong
authors.affiliation: Department of Molecular Physiology and Biophysics, Lester & Sue Smith Breast Center, Departments of Molecular and Cellular Biology and Radiology, and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA; Department of Systems Medicine and Bioengineering, The Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, Texas, USA; Department of Developmental Biology, Pittsburgh, Pennsylvania, USA; Women's Cancer Research Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Dickinson
authors.affiliation: Department of Molecular Physiology and Biophysics, Lester & Sue Smith Breast Center, Departments of Molecular and Cellular Biology and Radiology, and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA; Department of Systems Medicine and Bioengineering, The Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, Texas, USA; Department of Developmental Biology, Pittsburgh, Pennsylvania, USA; Women's Cancer Research Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Rosen
authors.affiliation: Department of Molecular Physiology and Biophysics, Lester & Sue Smith Breast Center, Departments of Molecular and Cellular Biology and Radiology, and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA; Department of Systems Medicine and Bioengineering, The Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, Texas, USA; Department of Developmental Biology, Pittsburgh, Pennsylvania, USA; Women's Cancer Research Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lewis
authors.affiliation: Department of Molecular Physiology and Biophysics, Lester & Sue Smith Breast Center, Departments of Molecular and Cellular Biology and Radiology, and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA; Department of Systems Medicine and Bioengineering, The Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, Texas, USA; Department of Developmental Biology, Pittsburgh, Pennsylvania, USA; Women's Cancer Research Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA vadakkan@bcm.edu meizhang@pitt.edu.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply* / Q000235:genetics / Q000473:pathology; D000818:Animals; D001808:Blood Vessels / Q000473:pathology*; D015687:Cell Hypoxia; D058948:Cell Tracking / Q000379:methods; D005260:Female; D017930:Genes, Reporter; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D064593:Heterografts; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018613:Microscopy, Confocal; D036641:Microscopy, Fluorescence, Multiphoton; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D014161:Transduction, Genetic; D064726:Triple Negative Breast Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency* / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016159:Tumor Suppressor Protein p53; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins
keywords: Cancer stem cells; In vivo optical imaging; Microvasculature; Signal transduction; Stem cell microenvironment; p53