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CD66+ cells in cervical precancers are partially differentiated progenitors with neoplastic traits.
Pattabiraman, Chitra; Hong, Shiyuan; Gunasekharan, Vignesh K; Pranatharthi, Annapurna; Bajaj, Jeevisha; Srivastava, Sweta; Krishnamurthy, H; Ammothumkandy, Aswathy; Giri, Venkat G; Laimins, Laimonis A; Krishna, Sudhir.
Afiliação
  • Pattabiraman C; National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS-GKVK Campus, Bangalore, Karnataka, India.
  • Hong S; Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
  • Gunasekharan VK; Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
  • Pranatharthi A; National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS-GKVK Campus, Bangalore, Karnataka, India.
  • Bajaj J; National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS-GKVK Campus, Bangalore, Karnataka, India.
  • Srivastava S; National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS-GKVK Campus, Bangalore, Karnataka, India.
  • Krishnamurthy H; National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS-GKVK Campus, Bangalore, Karnataka, India.
  • Ammothumkandy A; National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS-GKVK Campus, Bangalore, Karnataka, India.
  • Giri VG; Department of Radiotherapy, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India.
  • Laimins LA; Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
  • Krishna S; National Centre for Biological Sciences, Tata Institute of Fundamental Research, UAS-GKVK Campus, Bangalore, Karnataka, India. skrishna@ncbs.res.in.
Cancer Res ; 74(22): 6682-92, 2014 Nov 15.
Article em En | MEDLINE | ID: mdl-25267065
ABSTRACT
Cervical cancers, a malignancy associated with oncogenic papilloma viruses, remain a major disease burden in the absence of effective implementation of preventive strategies. CD66(+) cells have previously been identified as a tumor-propagating subset in cervical cancers. We investigated the existence, differentiation state, and neoplastic potential of CD66(+) cells in a precancer cell line harboring HPV31b episomes. The gene expression profile of CD66(high) cells overlaps with differentiated keratinocytes, neoplastic mesenchymal transition, cells of the squamocolumnar junction, and cervical cancer cell line-derived spheroids. There is elevated expression of DNMT1, Notch1, and the viral gene product E1⁁E4 in CD66(high) cells. Thus, CD66(high) cells, in the absence of differentiating signals, express higher levels of key regulators of keratinocytes stemness, differentiation, and the viral life cycle, respectively. We also find a striking association of neoplastic traits, including migration, invasion, and colony formation, in soft agar with CD66(high) cells. These properties and a distinct G2-M-enriched cell-cycle profile are conserved in cells from cervical cancers. Principally, using a precancerous cell line, we propose that CD66(high) cells have an intermediate differentiation state, with a cellular milieu connected with both viral replication and neoplastic potential, and validate some key features in precancer lesions. Such pathophysiologically relevant systems for defining cellular changes in the early phases of the disease process provide both mechanistic insight and potential therapeutic strategies. Collectively, our data provide a rationale for exploring novel therapeutic targets in CD66(+) subsets during cancer progression.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Lesões Pré-Cancerosas / Células-Tronco Neoplásicas / Antígenos CD / Moléculas de Adesão Celular / Neoplasias do Colo do Útero Limite: Female / Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Lesões Pré-Cancerosas / Células-Tronco Neoplásicas / Antígenos CD / Moléculas de Adesão Celular / Neoplasias do Colo do Útero Limite: Female / Humans Idioma: En Ano de publicação: 2014 Tipo de documento: Article