Effect of naive and cancer-educated fibroblasts on colon cancer cell circadian growth rhythm.
Alessia ParascandoloRaffaella BonavitaRosario AstaburuagaAntonio SciutoStefano ReggioEnrica BarraFrancesco CorcioneMarco SalvatoreGianluigi MazzoccoliAngela RelógioMikko O LaukkanenPublished in: Cell death & disease (2020)
Opportunistic modification of the tumour microenvironment by cancer cells enhances tumour expansion and consequently eliminates tumour suppressor components. We studied the effect of fibroblasts on the circadian rhythm of growth and protein expression in colon cancer HCT116 cells and found diminished oscillation in the proliferation of HCT116 cells co-cultured with naive fibroblasts, compared with those co-cultured with tumour-associated fibroblasts (TAFs) or those cultured alone, suggesting that TAFs may have lost or gained factors that regulate circadian phenotypes. Based on the fibroblast paracrine factor analysis, we tested IL6, which diminished HCT116 cell growth oscillation, inhibited early phase cell proliferation, increased early phase expression of the differentiation markers CEA and CDX2, and decreased early phase ERK5 phosphorylation. In conclusion, our data demonstrate how the cancer education of naive fibroblasts influences the circadian parameters of neighbouring cancer cells and highlights a putative role for IL6 as a novel candidate for preoperative treatments.
Keyphrases
- cell cycle arrest
- pi k akt
- extracellular matrix
- cell proliferation
- induced apoptosis
- signaling pathway
- cell death
- papillary thyroid
- endothelial cells
- hiv infected
- healthcare
- atrial fibrillation
- stem cells
- high frequency
- poor prognosis
- heart rate
- squamous cell
- blood pressure
- cell cycle
- patients undergoing
- endoplasmic reticulum stress
- machine learning
- big data
- squamous cell carcinoma
- quality improvement
- data analysis