TY - JOUR
T1 - Effect of naive and cancer-educated fibroblasts on colon cancer cell circadian growth rhythm
AU - Parascandolo, Alessia
AU - Bonavita, Raffaella
AU - Astaburuaga, Rosario
AU - Sciuto, Antonio
AU - Reggio, Stefano
AU - Barra, Enrica
AU - Corcione, Francesco
AU - Salvatore, Marco
AU - Mazzoccoli, Gianluigi
AU - Relógio, Angela
AU - Laukkanen, Mikko O.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41419-020-2468-2
DO - 10.1038/s41419-020-2468-2
M3 - Article
C2 - 32341349
AN - SCOPUS:85083972242
VL - 11
JO - Cell Death and Disease
JF - Cell Death and Disease
SN - 2041-4889
IS - 4
M1 - 289
ER -