We look inside the cells and understand how they become cancerous
IGC/DICYT A study in Barrett's esophagus condition unveiled the role of centrosomes, tiny structures that are smaller than a hair divided hundreds of times, in the development of esophageal cancer. Understanding the centrosomes we can know how this cancer begins. Cells begin to accumulate centrosomes-organelles that play a vital role during cell division-before they transform into cancer cells. Understanding the contribution of centrosomes to this process may lead in better treatments.
The research, which took place at Instituto Gulbenkian de Ciência (IGC) and the Instituto Português de Oncologia Francisco Gentil (IPO Lisbon), was published in the Journal of Cell Biology and suggests that centrosome amplification may contribute to the initiation and progression of a variety of human cancers.
The genomic instability created by excess centrosomes may help cancer cells to become more malignant. "Centrosome amplification is found in human tumors but not in normal cells, so it is an appealing feature to explore for diagnosis, prognosis and therapy," explains Carla Lopes, from IGC.
Mónica Bettencourt-Dias, from IGC, and Paula Chaves, from IPO Lisboa, investigated the role of centrosome amplification in tumorigenesis by examining samples from patients with Barrett's esophagus, a condition that increases the risk of development of esophageal cancer. In chronic acid reflux, epithelial cells lining the esophagus are replaced by cells usually found only in the stomach and intestine.
In a small percentage of patients, these "metaplastic" cells become dysplastic and proliferate abnormally, eventually giving rise to esophageal adenocarcinoma. By studying biopsies of patients with Barrett's esophagus under vigilance, the researchers could observe that the number of centrosomes increases in the cases that evolve to cancer. Therefore, extra centrosomes could be observed in "metaplastic" and pre-malignant cells of patients that developed the carcinoma.
"Given the widespread occurrence of mutations and centrosome amplification in human tumors, our findings on the timing and ordering of these events in Barrett's esophagus tumorigenesis can contribute to better understand the role of centrosomes in other cancers as well," says Marta Mesquita, from IPO Lisboa.
|*Lopes, C.A.M., Mesquita, M., Cunha, A.I., Cardoso, J., Carapeta, S., Laranjeira, C., Pinto, A.E., Pereira-Leal, J.B., Dias-Pereira, A. Bettencourt-Dias, M., Chaves, P. (2018) Centrosome amplification arises before neoplasia and increases upon p53 loss in tumorigenesis. Journal of Cell Biology. DOI: 10.1083/jcb.201711191.