Logarithmic expansion of LGR5(+) cells in human colorectal cancer Journal Article

Authors: Martin, M. L.; Zeng, Z.; Adileh, M.; Jacobo, A.; Li, C.; Vakiani, E.; Hua, G.; Zhang, L.; Haimovitz-Friedman, A.; Fuks, Z.; Kolesnick, R.; Paty, P. B.
Article Title: Logarithmic expansion of LGR5(+) cells in human colorectal cancer
Abstract: Stem cells of the small and large intestine are marked by expression of the Wnt target gene LGR5, a leucine-rich-repeat-containing G protein-coupled receptor. Previous studies reported increased expression of LGR5 in human colorectal cancer (CRC) compared to normal tissue either by immunohistochemistry or in situ hybridization (ISH). However, as these studies were semi-quantitative they did not provide a numerical estimate of the magnitude of this effect. While we confirm that LGR5+ cells are exclusively located at the base of normal human small and large intestinal crypts, representing approximately 6% of total crypt cells, we show this cell population is 10-fold expanded in all grades of CRC, representing as much as 70% of the cells of tumor crypt-like structures. This expansion of the LGR5 compartment coincides with maintenance of crypt-like glandular structure (adenomas, and well and moderately differentiated adenocarcinomas), and is reduced in poorly differentiated CRC, where crypt-like glandular architecture is lost, accompanied by reduced epithelial terminal differentiation. Altogether these results indicate that LGR5+ cell expansion is a hallmark of CRC tumorigenesis occurring during progression to adenoma, supporting CRC as a stem cell disease with implications for CRC therapy. © 2017 Elsevier Inc.
Keywords: immunohistochemistry; clinical article; controlled study; human tissue; protein expression; human cell; cancer growth; cancer grading; colorectal cancer; gene; gene targeting; cell structure; gene expression; tumor differentiation; cell population; uvomorulin; colorectal carcinoma; in situ hybridization; quantitative analysis; colorectal adenoma; tumor cell; cellular distribution; stem cells; colon carcinogenesis; intestine crypt; intestine mucosa; stem cell expansion; crypt cell; human; priority journal; article; lgr5+; lgr5 gene; lgr5+ stem cell line
Journal Title: Cellular Signalling
Volume: 42
ISSN: 0898-6568
Publisher: Elsevier Inc.  
Date Published: 2018-01-01
Start Page: 97
End Page: 105
Language: English
DOI: 10.1016/j.cellsig.2017.09.018
PROVIDER: scopus
PUBMED: 28958617
PMCID: PMC5766032
Notes: Article -- Export Date: 4 December 2017 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Zvi Fuks
    293 Fuks
  2. Philip B Paty
    367 Paty
  3. Zhaoshi Zeng
    82 Zeng
  4. Richard N Kolesnick
    230 Kolesnick
  5. Guoqiang Hua
    16 Hua
  6. Efsevia Vakiani
    162 Vakiani
  7. Maria Laura Martin
    8 Martin
  8. Lixing   Zhang
    2 Zhang
  9. Mohammad   Adileh
    2 Adileh
  10. Christy Y Li
    1 Li