CD66+ cells in cervical precancers are partially differentiated progenitors with neoplastic traits

Chitra Pattabiraman, Shiyuan Hong, Vignesh K. Gunasekharan, Annapurna Pranatharthi, Jeevisha Bajaj, Sweta Srivastava, H. Krishnamurthy, Aswathy Ammothumkandy, Venkat G. Giri, Laimonis A. Laimins, Sudhir Krishna*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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 CD66high 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, CD66high 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 CD66high 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 CD66high 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.

Original languageEnglish (US)
Pages (from-to)6682-6692
Number of pages11
JournalCancer Research
Volume74
Issue number22
DOIs
StatePublished - Nov 15 2014

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'CD66+ cells in cervical precancers are partially differentiated progenitors with neoplastic traits'. Together they form a unique fingerprint.

Cite this