A basal cell defect promotes budding of prostatic intraepithelial neoplasia
AffiliationUniv Arizona, Ctr Canc, Coll Med, Dept Cellular & Mol Med
Univ Arizona, Ctr Canc, Dept Pathol, Coll Med
MetadataShow full item record
PublisherCOMPANY OF BIOLOGISTS LTD
CitationA basal cell defect promotes budding of prostatic intraepithelial neoplasia 2017, 130 (1):104 Journal of Cell Science
JournalJournal of Cell Science
Rights© 2017. Published by The Company of Biologists Ltd
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractBasal 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 alpha 6 beta 4 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 alpha 6 beta 4 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 alpha 6 beta 4 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. beta 4-integrin-defective 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 (beta 4 integrin), laminin-332 or abnormal luminal expansion during HG-PIN progression.
Note12 month embargo; Posted online September 08, 2016.
VersionFinal published version
SponsorsNational Institutes of Health (NIH) [CA159406, P30 CA 23074]; NIH Search Results National Institute of General Medical Sciences (NIGMS) [R01GFM110166, MCB1158151]; Phoenix Friends of the UA Cancer Center