The number and size of tiny structures that exist inside cells, called centrioles, are increased in the most aggressive sub-types of cancer, researchers from Instituto Gulbenkian de Ciencia in Portugal found.
About 100 times smaller than the cross section of a hair, centrioles have been called the cells “brain”, as they play crucial roles in cell multiplication, movement and communication. Their number and size are highly controlled in normal cells.
Since their discovery, more than one century ago, it has been proposed that an abnormal increase in the number of these structures may induce cancer.
Cancer is a very diverse disease with some tumours being more aggressive and more resistant to chemotherapy than others. Clinicians are eager to find novel diagnostic, prognostic and treatment tools that allow them to predict outcomes and treat patients in a more personalised way. These findings may contribute to this process.
The research team, led by Monica Bettencourt Dias, investigated the incidence of centriole abnormalities in human cancer cells. The researchers thoroughly analysed a panel of 60 human cancer lines originated from 9 distinct tissues.
Their results reveal that cancer cells often have extra and longer centrioles, which are absent in normal cells.
Cellular consequences of centriole length deregulation. Credit: Gaëlle Marteil, et al. CC-BY
Importantly, the research team observed that supernumerary centrioles are more prevalent in aggressive breast – as the triple negative – and colon cancer. Also, the team discovered that longer centrioles are excessively active, which perturbs cell division and could favour cancer formation.
“Our data confirm that deregulated number and size of centrioles inside cells is associated with malignant features. This finding may help establishing centriole properties as a way of classifying tumours in order to establish prognosis and predict treatment response,”
said Gaelle Marteil, first author of this study and researcher at Bettencourt-Dias laboratory.
The human breast tumour samples used were consecutively retrieved from the files of the Department of Pathology, Hospital Xeral-Cies, Vigo, Spain. According to their immunoprofile, breast tumour samples were classified as luminal (ER+, PR+, HER2− and Ki67−) or basal-like carcinomas (ER−, PR−, HER2−, basal marker+).
Imaging was performed on a Zeiss Imager Z1 inverted microscope, equipped with an AxioCam MRm camera (Zeiss) and ApoTome (Zeiss), using the ×100 1.4 NA Oil immersion objective.
Quantifying centriole number and length in cancer cells Credit: Gaëlle Marteil, et al. CC-BY
The study identified a novel cause of centriole amplification in cancer, centriole over-elongation. This defect affects only a subpopulation of cells, therefore reflecting inter-cellular heterogeneity that can reflect a dynamic equilibrium between genesis and death of cells with centriole over-elongation.
The study involved an international research team from Instituto Gulbenkian de Ciencia, I3S- Instituto de Investigação e Inovação em Saúde (Portugal), IPATIMUP – Instituto de Patologia e Imunologia Molecular (Portugal), Instituto de Medicina Molecular (Portugal), Instituto Portugues de Oncologia (Portugal), and Dana-Faber Cancer Institute (USA). The work was funded by European Research Council (ERC), European Molecular Biology Organization (EMBO), Fundação para a Ciencia e a Tecnologia (FCT, Portugal), and FCT- Harvard Medical School Program Portugal.
Gaëlle Marteil, Adan Guerrero, André F. Vieira, Bernardo P. de Almeida, Pedro Machado, Susana Mendonça, Marta Mesquita, Beth Villarreal, Irina Fonseca, Maria E. Francia, Katharina Dores, Nuno P. Martins, Swadhin C. Jana, Erin M. Tranfield, Nuno L. Barbosa-Morais, Joana Paredes, David Pellman, Susana A. Godinho & Mónica Bettencourt-Dias Over-elongation of centrioles in cancer promotes centriole amplification and chromosome missegregation Nature Communications volume 9, Article number: 1258 (2018) doi:10.1038/s41467-018-03641-x
Top Image: Gaëlle Marteil, IGC. Healthy cells (left) display four centrioles, a normal number (in yellow). Breast cancer cells (triple negative) have extra centrioles (here 16, right image).