A basal cell defect promotes budding of prostatic intraepithelial neoplasia

Mengdie Wang, Raymond B. Nagle, Beatrice S. Knudsen, Gregory C. Rogers, Anne E. Cress

Research output: Contribution to journalArticle

Abstract

Basal cells in a simple secretory epithelium adhere to the extracellular matrix (ECM), providing contextual cues for ordered repopulation of the luminal cell layer. Early high-grade prostatic intraepithelial neoplasia (HG-PIN) tissue has enlarged nuclei and nucleoli, luminal layer expansion and genomic instability. Additional HG-PIN markers include loss of α6β4 integrin or its ligand laminin-332, and budding of tumor clusters into laminin-511-rich stroma. We modeled the invasive budding phenotype by reducing expression of αa6β4 integrin in spheroids formed from two normal human stable isogenic prostate epithelial cell lines (RWPE-1 and PrEC 11220). These normal cells continuously spun in culture, forming multicellular spheroids containing an outer laminin-332 layer, basal cells (expressing αa6β4 integrin, high-molecular-weight cytokeratin and p63, also known as TP63) and luminal cells that secrete PSA (also known as KLK3). Basal cells were optimally positioned relative to the laminin-332 layer as determined by spindle orientation. β4-integrindefective spheroids contained a discontinuous laminin-332 layer corresponding to regions of abnormal budding. This 3D model can be readily used to study mechanisms that disrupt laminin-332 continuity, for example, defects in the essential adhesion receptor (β4 integrin), laminin-332 or abnormal luminal expansion during HG-PIN progression.

LanguageEnglish (US)
Pages104-110
Number of pages7
JournalJournal of Cell Science
Volume130
Issue number1
DOIs
StatePublished - 2017

Fingerprint

Prostatic Intraepithelial Neoplasia
Integrins
Cellular Spheroids
Genomic Instability
Keratins
Cues
Extracellular Matrix
kalinin
Prostate
Epithelium
Molecular Weight
Epithelial Cells
Ligands
Phenotype
Cell Line

Keywords

  • Integrin
  • Laminin
  • Neoplasia
  • Prostate
  • Spheroids

ASJC Scopus subject areas

  • Cell Biology

Cite this

A basal cell defect promotes budding of prostatic intraepithelial neoplasia. / Wang, Mengdie; Nagle, Raymond B.; Knudsen, Beatrice S.; Rogers, Gregory C.; Cress, Anne E.

In: Journal of Cell Science, Vol. 130, No. 1, 2017, p. 104-110.

Research output: Contribution to journalArticle

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