TY - JOUR
T1 - The interplay between colon cancer cells and tumour-associated stromal cells impacts the biological clock and enhances malignant phenotypes
AU - Fuhr, Luise
AU - Abreu, Mónica
AU - Carbone, Annalucia
AU - El-Athman, Rukeia
AU - Bianchi, Fabrizio
AU - Laukkanen, Mikko O.
AU - Mazzoccoli, Gianluigi
AU - Relógio, Angela
PY - 2019/7/1
Y1 - 2019/7/1
N2 - Cancer cells interrelate with the bordering host microenvironment that encompasses the extracellular matrix and a nontumour cellular component comprising fibroblasts and immune-competent cells. The tumour microenvironment modulates cancer onset and progression, but the molecular factors managing this interaction are not fully understood. Malignant transformation of a benign tumour is among the first crucial events in colorectal carcinogenesis. The role of tumour stroma fibroblasts is well-described in cancer, but less well-characterized in benign tumours. In the current work we utilized fibroblasts isolated from tubulovillous adenoma, which has high risk for malignant transformation, to study the interaction between benign tumour stroma and the circadian clock machinery. We explored the role of the biological clock in this interplay taking advantage of an experimental model, represented by the co-culture of colon cancer cells with normal fibroblasts or tumour-associated fibroblasts, isolated from human colorectal tumour specimens. When co-cultured with tumour-associated fibroblasts, colon cancer cells showed alterations in their circadian and metabolic parameters, with decreased apoptosis, increased colon cancer cell viability, and increased resistance to chemotherapeutic agents. In conclusion, the interactions among colon cancer cells and tumour-associated fibroblasts affect the molecular clockwork and seem to aggravate malignant cell phenotypes, suggesting a detrimental effect of this interplay on cancer dynamics.
AB - Cancer cells interrelate with the bordering host microenvironment that encompasses the extracellular matrix and a nontumour cellular component comprising fibroblasts and immune-competent cells. The tumour microenvironment modulates cancer onset and progression, but the molecular factors managing this interaction are not fully understood. Malignant transformation of a benign tumour is among the first crucial events in colorectal carcinogenesis. The role of tumour stroma fibroblasts is well-described in cancer, but less well-characterized in benign tumours. In the current work we utilized fibroblasts isolated from tubulovillous adenoma, which has high risk for malignant transformation, to study the interaction between benign tumour stroma and the circadian clock machinery. We explored the role of the biological clock in this interplay taking advantage of an experimental model, represented by the co-culture of colon cancer cells with normal fibroblasts or tumour-associated fibroblasts, isolated from human colorectal tumour specimens. When co-cultured with tumour-associated fibroblasts, colon cancer cells showed alterations in their circadian and metabolic parameters, with decreased apoptosis, increased colon cancer cell viability, and increased resistance to chemotherapeutic agents. In conclusion, the interactions among colon cancer cells and tumour-associated fibroblasts affect the molecular clockwork and seem to aggravate malignant cell phenotypes, suggesting a detrimental effect of this interplay on cancer dynamics.
KW - Biological clock
KW - Cancer
KW - Colorectal
KW - Tumour stroma
UR - http://www.scopus.com/inward/record.url?scp=85071194221&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071194221&partnerID=8YFLogxK
U2 - 10.3390/cancers11070988
DO - 10.3390/cancers11070988
M3 - Article
AN - SCOPUS:85071194221
VL - 11
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 7
M1 - 988
ER -