Friday, 26 January 2018 15:04

The number of mitochondria in a tumour cell predicts its sensitivity to chemotherapy

HeLa cells in which mitochondria are stained green.  The image was acquired 12 hours after cell exposure to the chemotherapeutic drug TRIAL.  Dead cells (rounded) have a larger number of mitochondria than live cells HeLa cells in which mitochondria are stained green. The image was acquired 12 hours after cell exposure to the chemotherapeutic drug TRIAL. Dead cells (rounded) have a larger number of mitochondria than live cells Francisco Iborra, CNB-CSIC

Tumour cells with a large number of mitochondria are more sensitive to chemotherapy. This might explain why some cells die after anti-tumour treatment while others that are genetically identical can survive and cause the cancer to reappear. Mitochondria number might be used to predict patient sensitivity to a specific treatment.

One of the main problems of chemotherapy is the resistance of some patients to treatment.  This is because the therapy is not effective against all tumour cells; some survive and are able to regenerate the tumour.

A study published in the journal Nature Communications shows that variations in the number of mitochondria –the energy factories in the cells of higher organisms– might cause the distinct sensitivity of genetically identical cells to the same anti-tumour treatment.  The work was carried out by scientists at the Centro Nacional de Biotecnología of the CSIC (CNB-CSIC), in collaboration with the Universidad Autónoma de Madrid and the Hospitals of Torrevieja and Vinalopó (Alicante).

Differences in sensitivity to chemotherapy have traditionally been associated with genetic variation, although identical cells sometimes respond differently to the same treatment.  "Not everything is determined by genetics.  The internal and external context have great influence on the cell,” explains Francisco Iborra, director of study and CNB-CSIC scientist.  “Our results indicate that only cells with a large number of mitochondria respond to treatment."

This finding could offer new tools for selecting which therapy to assign to a specific patient.  "To date, we lacked biomarkers that could be used to predict the tumour cell response to conventional treatments.  We think that mitochondrial mass could be a good indicator of prognosis, and predict whether a treatment will be effective against a certain cancer," explains Iborra.

The reason that some cells have more mitochondria than others is unequal distribution during cell division.  One of the daughter cells usually receives more mitochondria from the progenitor cell.  The results of this study indicate that cells with more mitochondria have more apoptotic proteins –inducers of cell death.  In this way, cells with greater mitochondrial content are more prone to death from anti-tumour drugs.

At the moment, the study has been carried out on tumour cells in in vitro culture.  Analyses of colon cancer biopsies support the hypothesis of a correlation between mitochondrial mass and the proteins that induce cell death.  "Now we are beginning the second part of the study –validating the results in samples of different types of tumours, with different drugs.  This will corroborate whether these observations can be extrapolated to clinical use," explains Iborra.


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