Abstract 1136: Decrease in maturation of stem cells along the neuroendocrine lineage contributes to stem cell overpopulation that drives human CRC development

• Published in: Cancer research (Chicago, Ill.) Ill.), 2018-07, Vol.78 (13_Supplement), p.1136-1136
• Main Authors: Boman, Bruce M., Zhang, Tao, Modarai, Shirin, Opdenacker, Lynn, Jeremy, Fields
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2018-1136

Stem cell (SC) overpopulation is thought to drive tumor initiation and progression during colon cancer development, but it is unclear what causes the SC overpopulation. Because most neuroendocrine (NE) cells (NECs) in normal colonic crypts reside within the SC niche at the crypt bottom, we thought that aberrant NECs might be linked to the SC overpopulation. We hypothesized that (i) in normal crypts, SC and NEC populations are anatomically and functionally related, and (ii) during tumorigenesis, changes in these relationships quantitatively correlate with increased SC numbers. We tested this hypothesis - using quantitative immunohistochemical mapping - as a first step towards understanding how interactions between SC and NEC might become altered during colon tumorigenesis. In normal human colonic crypts, most (>80%) cells staining for ALDH1, a colonic SC marker, co-stained for chromogranin-A (CGA) and several other NE markers. Neither ALDH1+ nor CGA+ cells co-stained for MCM2, a marker for proliferating cells. These findings indicate that, in normal colonic crypts, many ALDH1+ cells have NE characteristics. In contrast, the proportion of ALDH1+ cells that co-stained for NE markers progressively decreased (to