title: Immunohistochemical analysis of differentiation in static and mixed prostate cancer spheroids.
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 micro m 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.
authors.affiliation: Department of Chemical Engineering, Tulane University, Lindy Boggs Center, Suite 300, New Orleans, Louisiana 70118, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Song
authors.forename: Kim C
authors.initials: KC
authors.lastname: O'Connor
authors.forename: Odile
authors.initials: O
authors.lastname: David
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Giordano
authors.forename: Helena
authors.initials: H
authors.lastname: Pappas-LeBeau
authors.forename: Sanda
authors.initials: S
authors.lastname: Clejan
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000378:metabolism; D008297:Male; D051379:Mice; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D018874:Spheroids, Cellular / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D007633:Keratins; D017430:Prostate-Specific Antigen