The interplay between colon cancer cells and tumour-associated stromal cells impacts the biological clock and enhances malignant phenotypes

Luise Fuhr, Mónica Abreu, Annalucia Carbone, Rukeia El-Athman, Fabrizio Bianchi, Mikko O. Laukkanen, Gianluigi Mazzoccoli, Angela Relógio

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number988
JournalCancers
Volume11
Issue number7
DOIs
Publication statusPublished - Jul 1 2019

Keywords

  • Biological clock
  • Cancer
  • Colorectal
  • Tumour stroma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'The interplay between colon cancer cells and tumour-associated stromal cells impacts the biological clock and enhances malignant phenotypes'. Together they form a unique fingerprint.

Cite this