title: Contextual niche signals towards colorectal tumor progression by mesenchymal stem cell in the mouse xenograft model.
abstract: BACKGROUND
  The role of mesenchymal stem/stromal cells (MSCs) in tumorigenesis remains controversial. This study aimed to determine whether heterotypic interactions between MSCs and colon cancer cells can supply contextual signals towards tumor progression.
  
  
  METHODS
  Xenografts consisting of co-implanted human colorectal cancer cells with rat MSCs in immunodeficient mice were evaluated by tumor progression, angiogenic profiles, and MSC fate. Furthermore, we investigated how MSCs function as a cancer cell niche by co-culture experiments in vitro.
  
  
  RESULTS
  Tumor growth progressed in two ways, either independent of or dependent on MSCs. Such cell line-specific dependency could not be explained by host immune competency. COLO 320 xenograft angiogenesis was MSC-dependent, but less dependent on vascular endothelial growth factor (VEGF), whereas HT-29 angiogenesis was not MSC-dependent, but was VEGF-dependent. MSCs and COLO 320 cells established a functional positive feedback loop that triggered formation of a cancer cell niche, leading to AKT activation. Subsequently, MSCs differentiated into pericytes that enhanced angiogenesis as a perivascular niche. In contrast, the MSC niche conferred an anti-proliferative property to HT-29 cells, through mesenchymal-epithelial transition resulting in p38 activation.
  
  
  CONCLUSIONS
  In conclusion, MSCs demonstrate pleiotropic capabilities as a cancer cell or perivascular niche to modulate colorectal cancer cell fate in a cell line-dependent manner in a xenogeneic context.
authors: Department of Gastroenterology, Rheumatology, and Clinical Immunology, Sapporo Medical University, Sapporo, 060-8543, Japan.
authors: Suguru
authors: S
authors: Nakagaki
authors: Yoshiaki
authors: Y
authors: Arimura
authors: Kanna
authors: K
authors: Nagaishi
authors: Hiroyuki
authors: H
authors: Isshiki
authors: Masanao
authors: M
authors: Nasuno
authors: Shuhei
authors: S
authors: Watanabe
authors: Masashi
authors: M
authors: Idogawa
authors: Kentaro
authors: K
authors: Yamashita
authors: Yasuyoshi
authors: Y
authors: Naishiro
authors: Yasushi
authors: Y
authors: Adachi
authors: Hiromu
authors: H
authors: Suzuki
authors: Mineko
authors: M
authors: Fujimiya
authors: Kohzoh
authors: K
authors: Imai
authors: Yasuhisa
authors: Y
authors: Shinomura
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D015179:Colorectal Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D064593:Heterografts; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D051379:Mice; D046228:Microarray Analysis; D009385:Neoplastic Processes; D009389:Neovascularization, Pathologic / Q000473:pathology*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D055153:Stem Cell Niche / Q000502:physiology*; D014183:Transplantation, Heterologous