title: Identification of a population of epidermal squamous cell carcinoma cells with enhanced potential for tumor formation.
abstract: Epidermal squamous cell carcinoma is among the most common cancers in humans. These tumors are comprised of phenotypically diverse populations of cells that display varying potential for proliferation and differentiation. An important goal is identifying cells from this population that drive tumor formation. To enrich for tumor-forming cells, cancer cells were grown as spheroids in non-attached conditions. We show that spheroid-selected cells form faster growing and larger tumors in immune-compromised mice as compared to non-selected cells. Moreover, spheroid-selected cells gave rise to tumors following injection of as few as one hundred cells, suggesting these cells have enhanced tumor-forming potential. Cells isolated from spheroid-selected tumors retain an enhanced ability to grow as spheroids when grown in non-attached culture conditions. Thus, these tumor-forming cells retain their phenotype following in vivo passage as tumors. Detailed analysis reveals that spheroid-selected cultures are highly enriched for expression of epidermal stem cell and embryonic stem cell markers, including aldehyde dehydrogenase 1, keratin 15, CD200, keratin 19, Oct4, Bmi-1, Ezh2 and trimethylated histone H3. These studies indicate that a subpopulation of cells that possess stem cell-like properties and express stem cell markers can be derived from human epidermal cancer cells and that these cells display enhanced ability to drive tumor formation.
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Gautam
authors.initials: G
authors.lastname: Adhikary
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Dan
authors.initials: D
authors.lastname: Grun
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Candace
authors.initials: C
authors.lastname: Kerr
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Sivaprakasam
authors.initials: S
authors.lastname: Balasubramanian
authors.affiliation: Department of Microbiology and Immunology, The University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Rorke
authors.affiliation: Life Technologies, Inc. Stem Cell Technologies, Frederick, Maryland, United States of America.
authors.forename: Mohan
authors.initials: M
authors.lastname: Vemuri
authors.affiliation: Life Technologies, Inc. Stem Cell Technologies, Frederick, Maryland, United States of America.
authors.forename: Shayne
authors.initials: S
authors.lastname: Boucher
authors.affiliation: Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.
authors.forename: Jackie R
authors.initials: JR
authors.lastname: Bickenbach
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Maryland School of Medicine, Baltimore, Maryland, United States of America ; Department of Dermatology, The University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hornyak
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Wen
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Fisher
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Maryland School of Medicine, Baltimore, Maryland, United States of America ; Department of Dermatology, The University of Maryland School of Medicine, Baltimore, Maryland, United States of America ; Department of Reproductive Biology, The University of Maryland School of Medicine, Baltimore, Maryland, United States of America ; Department of Microbiology and Immunology, The University of Maryland School of Medicine, Baltimore, Maryland, United States of America ; The Marlene and Stewart Greenebaum Cancer Center, The University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Eckert
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000503:physiopathology*; D018929:Cell Culture Techniques / Q000379:methods; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D000078404:Epidermal Cells; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D014411:Neoplastic Stem Cells / Q000502:physiology*; D018874:Spheroids, Cellular / Q000166:cytology* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor