title: Tumor-initiating cells are rare in many human tumors.
abstract: Tumor-initiating cells (TICs) are defined by their ability to form tumors after xenotransplantation in immunodeficient mice and appear to be relatively rare in most human cancers. Recent data in melanoma indicate that the frequency of TICs increases dramatically via more permissive xenotransplantation conditions, raising the possibility that the true frequency of TICs has been greatly underestimated in most human tumors. We compared the growth of human pancreatic, non-small cell lung, and head and neck carcinomas in NOD/SCID and NSG mice. Although TIC frequency was detected up to 10-fold higher in NSG mice, it remained low (<1 in 2500 cells) in all cases. Moreover, aldehyde dehydrogenase-positive (ALDH(+)) and CD44(+)CD24(+) cells, phenotypically distinct cells enriched in TICs, were equally tumorigenic in NOD/SCID and NSG mice. Our findings demonstrate that TICs are rare in these cancers and that the identification of TICs and their frequency in other human malignancies should be validated via primary tumors and highly permissive xenotransplantation conditions.
authors.affiliation: Latner Thoracic Surgery Research Laboratories, Toronto General Research Institute, University of Toronto, University Health Network, Toronto, Ontario MG5 1L7, Canada.
authors.forename: Kota
authors.initials: K
authors.lastname: Ishizawa
authors.forename: Zeshaan A
authors.initials: ZA
authors.lastname: Rasheed
authors.forename: Robert
authors.initials: R
authors.lastname: Karisch
authors.forename: Qiuju
authors.initials: Q
authors.lastname: Wang
authors.forename: Jeanne
authors.initials: J
authors.lastname: Kowalski
authors.forename: Erica
authors.initials: E
authors.lastname: Susky
authors.forename: Keira
authors.initials: K
authors.lastname: Pereira
authors.forename: Christina
authors.initials: C
authors.lastname: Karamboulas
authors.forename: Nadeem
authors.initials: N
authors.lastname: Moghal
authors.forename: N V
authors.initials: NV
authors.lastname: Rajeshkumar
authors.forename: Manuel
authors.initials: M
authors.lastname: Hidalgo
authors.forename: Ming
authors.initials: M
authors.lastname: Tsao
authors.forename: Laurie
authors.initials: L
authors.lastname: Ailles
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Waddell
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Neel
authors.forename: William
authors.initials: W
authors.lastname: Matsui
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009369:Neoplasms / Q000209:etiology / Q000473:pathology*; D009374:Neoplasms, Experimental / Q000473:pathology*; D014183:Transplantation, Heterologous
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