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: Research - peer-reviewArticle

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
kalinin
Integrins
Cellular Spheroids
Genomic Instability
Keratins
Cues
Extracellular Matrix
Prostate
Epithelium
Molecular Weight
Epithelial Cells
Ligands
Phenotype
Cell Line
Neoplasms
laminin 10
adhesion receptor

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: Research - peer-reviewArticle

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