PUBLICATION

Adipose-derived mesenchymal stem cells promote the malignant phenotype of cervical cancer

Authors
Castro-Oropeza, R., Vazquez-Santillan, K., Díaz-Gastelum, C., Melendez-Zajgla, J., Zampedri, C., Ferat-Osorio, E., Rodríguez-González, A., Arriaga-Pizano, L., Maldonado, V.
ID
ZDB-PUB-210306-12
Date
2020
Source
Scientific Reports   10: 14205 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Animals
  • Carcinoma, Squamous Cell/etiology*
  • Carcinoma, Squamous Cell/metabolism
  • Carcinoma, Squamous Cell/mortality
  • Epithelial-Mesenchymal Transition
  • Female
  • HaCaT Cells
  • HeLa Cells
  • Humans
  • Mesenchymal Stem Cells/physiology*
  • NF-kappa B/metabolism*
  • Neovascularization, Pathologic
  • Obesity/complications*
  • Obesity/metabolism
  • Transcriptome
  • Uterine Cervical Neoplasms/etiology*
  • Uterine Cervical Neoplasms/metabolism
  • Uterine Cervical Neoplasms/mortality
  • Zebrafish
PubMed
32848147 Full text @ Sci. Rep.
Abstract
Epidemiological studies indicate that obesity negatively affects the progression and treatment of cervical-uterine cancer. Recent evidence shows that a subpopulation of adipose-derived stem cells can alter cancer properties. In the present project, we described for the first time the impact of adipose-derived stem cells over the malignant behavior of cervical cancer cells. The transcriptome of cancer cells cultured in the presence of stem cells was analyzed using RNA-seq. Changes in gene expression were validated using digital-PCR. Bioinformatics tools were used to identify the main transduction pathways disrupted in cancer cells due to the presence of stem cells. In vitro and in vivo assays were conducted to validate cellular and molecular processes altered in cervical cancer cells owing to stem cells. Our results show that the expression of 95 RNAs was altered in cancer cells as a result of adipose-derived stem cells. Experimental assays indicate that stem cells provoke an increment in migration, invasion, angiogenesis, and tumorigenesis of cancer cells; however, no alterations were found in proliferation. Bioinformatics and experimental analyses demonstrated that the NF-kappa B signaling pathway is enriched in cancer cells due to the influence of adipose-derived stem cells. Interestingly, the tumor cells shift their epithelial to a mesenchymal morphology, which was reflected by the increased expression of specific mesenchymal markers. In addition, stem cells also promote a stemness phenotype in the cervical cancer cells. In conclusion, our results suggest that adipose-derived stem cells induce cervical cancer cells to acquire malignant features where NF-kappa B plays a key role.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping