title: Nanoparticle-based sorting of circulating tumor cells by epithelial antigen expression during disease progression in an animal model.
abstract: Circulating tumor cells (CTCs) can be used as markers for the detection, characterization, and targeted therapeutic management of cancer. We recently developed a nanoparticle-mediated approach for capture and sorting of CTCs based on their specific epithelial phenotype. In the current study, we investigate the phenotypic transition of tumor cells in an animal model and show the correlation of this transition with tumor progression. VX2 tumor cells were injected into rabbits, and CTCs were evaluated during tumor progression and correlated with computerized tomography (CT) measurements of tumor volume. The results showed a dramatic increase of CTCs during the four weeks of tumor growth. Following resection, CTC levels dropped but then rebounded, likely due to lymph node metastases. Additionally, CTCs showed a marked loss of the epithelial cell adhesion molecule (EpCAM) relative to precursor cells. In conclusion, the device accurately traces disease progression and CTC phenotypic shift in an animal model.
  
  
  BACKGROUND
  The detection of circulating tumor cells (CTCs) has been used to predict disease prognosis. In this study, the authors developed a nanoparticle-mediated platform based on microfluidics to analyze the differential expressions of epithelial cell adhesion molecule (EpCAM) on CTCs in an animal model. It was found that the loss of EpCAM correlated with disease progression. Hence, the use of this platform may be further applied in other cancer models in the future.
authors.affiliation: TECHNA Institute, University Health Network, Toronto; Department of Surgical Oncology, Princess Margaret Cancer Centre, Toronto; Department of Otolaryngology, Head and neck surgery, University of Toronto.
authors.forename: Nidal
authors.initials: N
authors.lastname: Muhanna
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
authors.forename: Adam
authors.initials: A
authors.lastname: Mepham
authors.affiliation: Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
authors.forename: Reza M
authors.initials: RM
authors.lastname: Mohamadi
authors.affiliation: TECHNA Institute, University Health Network, Toronto.
authors.forename: Harley
authors.initials: H
authors.lastname: Chan
authors.affiliation: TECHNA Institute, University Health Network, Toronto.
authors.forename: Tahsin
authors.initials: T
authors.lastname: Khan
authors.affiliation: TECHNA Institute, University Health Network, Toronto.
authors.forename: Margarete
authors.initials: M
authors.lastname: Akens
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
authors.forename: Justin D
authors.initials: JD
authors.lastname: Besant
authors.affiliation: TECHNA Institute, University Health Network, Toronto; Department of Surgical Oncology, Princess Margaret Cancer Centre, Toronto; Department of Otolaryngology, Head and neck surgery, University of Toronto. Electronic address: jonathan.irish@uhn.ca.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Irish
authors.affiliation: Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada. Electronic address: shana.kelley@utoronto.ca.
authors.forename: Shana O
authors.initials: SO
authors.lastname: Kelley
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000097:blood*; D015815:Cell Adhesion Molecules / Q000097:blood*; D045744:Cell Line, Tumor; D058948:Cell Tracking / Q000379:methods; D004195:Disease Models, Animal; D018450:Disease Progression; D000071858:Epithelial Cell Adhesion Molecule; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D008207:Lymphatic Metastasis; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D009369:Neoplasms / Q000097:blood* / Q000473:pathology / Q000628:therapy*; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D011817:Rabbits; D047368:Tumor Burden
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule
keywords: Cell sorting; Circulating tumor cells; Microfluidics; Nanoparticle; Rabbit cancer model