title: Characterization of Epithelial Progenitors in Normal Human Palatine Tonsils and Their HPV16 E6/E7-Induced Perturbation.
abstract: Human palatine tonsils are oropharyngeal lymphoid tissues containing multiple invaginations (crypts) in which the continuity of the outer surface epithelium is disrupted and the isolated epithelial cells intermingle with other cell types. We now show that primitive epithelial cells detectable in vitro in 2D colony assays and in a 3D culture system are CD44(+)NGFR(+) and present in both surface and crypt regions. Transcriptome analysis indicated a high similarity between CD44(+)NGFR(+) cells in both regions, although those isolated from the crypt contained a higher proportion of the most primitive (holo)clonogenic cells. Lentiviral transduction of CD44(+)NGFR(+) cells from both regions with human papillomavirus 16-encoded E6/E7 prolonged their growth in 2D cultures and caused aberrant differentiation in 3D cultures. Our findings therefore reveal a shared, site-independent, hierarchical organization, differentiation potential, and transcriptional profile of normal human tonsillar epithelial progenitor cells. They also introduce a new model for investigating the mechanisms of their transformation.
authors.affiliation: Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC V5A 1S6, Canada; Department of Cancer Control Research, British Columbia Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Sung Yoon Catherine
authors.initials: SYC
authors.lastname: Kang
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
authors.forename: Nagarajan
authors.initials: N
authors.lastname: Kannan
authors.affiliation: Faculty of Dentistry, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
authors.forename: Lewei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Integrative Oncology, British Columbia Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Victor
authors.initials: V
authors.lastname: Martinez
authors.affiliation: Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC V5A 1S6, Canada; Department of Cancer Control Research, British Columbia Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Miriam P
authors.initials: MP
authors.lastname: Rosin
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC V5Z 1L3, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada. Electronic address: ceaves@bccrc.ca.
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Eaves
mesh_terms: D000293:Adolescent; D000328:Adult; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D052162:Human papillomavirus 16 / Q000502:physiology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D014066:Palatine Tonsil / Q000166:cytology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D050725:Papillomavirus E7 Proteins / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000378:metabolism / Q000473:pathology*; D017475:Receptors, Nerve Growth Factor / Q000032:analysis; D012097:Repressor Proteins / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D059467:Transcriptome; D055815:Young Adult
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D018960:Hyaluronan Receptors; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D017475:Receptors, Nerve Growth Factor; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16
keywords: HPV; epithelial progenitors; oropharyngeal cancer; tonsil