Wnt and the cancer niche: paracrine interactions with gastrointestinal cancer cells undergoing asymmetric cell division

• Published in: Journal of Cancer Vol. 4; no. 6; pp. 447 - 457
• Main Authors: Xin, Hong-Wu, Ambe, Chenwi M, Ray, Satyajit, Kim, Bo-Kyu, Koizumi, Tomotake, Wiegand, Gordon W, Hari, Danielle, Mullinax, John E, Jaiswal, Kshama R, Garfield, Susan H, Stojadinovic, Alexander, Rudloff, Udo, Thorgeirsson, Snorri S, Avital, Itzhak
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher 01.01.2013
• Subjects: Research Paper; Microenvironment; Non-Random Chromosomal Cosegregation; Asymmetric Cell Division; Cancer Stem Cells
• ISSN: 1837-9664; 1837-9664
• DOI: 10.7150/jca.6896

Stem-like cancer cells contribute to cancer initiation and maintenance. Stem cells can self-renew by asymmetric cell division (ACD). ACD with non-random chromosomal cosegregation (ACD-NRCC) is one possible self-renewal mechanism. There is a paucity of evidence supporting ACD-NRCC in human cancer. Our aim was to investigate ACD-NRCC and its potential interactions with the cancer niche (microenvironment) in gastrointestinal cancers. We used DNA double and single labeling approaches with FACS to isolate live cells undergoing ACD-NRCC. Gastrointestinal cancers contain rare subpopulations of cells capable of ACD-NRCC. ACD-NRCC was detected preferentially in subpopulations of cells previously suggested to be stem-like/tumor-initiating cancer cells. ACD-NRCC was independent of cell-to-cell contact, and was regulated by the cancer niche in a heat-sensitive paracrine fashion. Wnt pathway genes and proteins are differentially expressed in cells undergoing ACD-NRCC vs. symmetric cell division. Blocking the Wnt pathway with IWP2 (WNT antagonist) or siRNA-TCF4 resulted in suppression of ACD-NRCC. However, using a Wnt-agonist did not increase the relative proportion of cells undergoing ACD-NRCC. Gastrointestinal cancers contain subpopulations of cells capable of ACD-NRCC. Here we show for the first time that ACD-NRCC can be regulated by the Wnt pathway, and by the cancer niche in a paracrine fashion. However, whether ACD-NRCC is exclusively associated with stem-like cancer cells remains to be determined. Further study of these findings might generate novel insights into stem cell and cancer biology. Targeting the mechanism of ACD-NRCC might engender novel approaches for cancer therapy.