Immunohistochemical analysis of differentiation in static and mixed prostate cancer spheroids

Hong Song, Kim C. O'Connor, Odile David, Carrie L. Giordano, Helena Pappas-LeBeau, Sanda Clejan

Research output: Contribution to journalArticlepeer-review

Abstract

Neoplastic multicellular spheroids are in vitro models of solid tumors employed in drug testing and basic research. This study compares differentiation in static and mixed prostate cancer spheroids. Staining intensity of prostate specific antigen (PSA) was down-regulated upon mixing, from 0.21 ± 0.03 to 0.13 ± 0.03 in LNCaP multicellular spheroids, and from 0.13 ± 0.04 to 0.03 ± 0.02 in DU 145 multicellular spheroids. This was accompanied by 65% increase in the expression of cytokeratins 8 and 18 in DU 145 spheroids. PSA expression extended 60 μm within static spheroids and was disrupted in mixed culture. Diminished PSA expression and spatial organization suggests a more aggressive cancer. Higher cytokeratin expression could result from either differentiation towards a luminal phenotype or activation of the Ras pathway during dedifferentiation. Thus, the existing paradigm of differentiation established for normal tissue does not apply for our neoplastic spheroids. Cell dedifferentiation is attributed to improved interstitial transport and synthesis of extracellular matrix.

Original languageEnglish (US)
Pages (from-to)180-186
Number of pages7
JournalJournal of Cellular and Molecular Medicine
Volume7
Issue number2
DOIs
StatePublished - 2003

Keywords

  • Cytokeratins
  • Differentiation
  • Mixing
  • PSA
  • Prostate cancer
  • Spheroid

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

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