Mitochondrial Changes Seen in Malignant Mesotheliomas Might Offer Way of Treating Aggressive Cancer

A study using mathematical analysis of mitochondrial morphology in malignant mesothelioma found that inhibiting mitochondria might be an effective treatment strategy against the deadly cancer — and suggested that the appearance of mitochondria might predict the response to such inhibition. The findings indicated that selectively blocking mitochondria might be a promising new treatment approach for malignant mesothelioma.

Mesothelioma tumors are not easily quantified by size and volume, and so the study, “Unique fractal evaluation and therapeutic implications of mitochondrial morphology in malignant mesothelioma,“ used an unconventional method to assess the tumors.

Fractals are mathematical constructs, which display repeated patterns of self-similarity over an infinite scale. Scientists believe that many biological structures possess such properties, and fractal dimension measurements can be used to assess the complexity and space-filling properties of a shape. Another measure, often used in combination with fractal measurements, is lacunarity, which describes the texture of a shape or fractal.

Researchers at the University of Chicago used these measurements to assess differences between benign and malignant mesothelioma tissue, specifically looking at the appearance of mitochondria in cultured cells derived from tumors. (Malignant mesothelioma is an aggressive cancer, usually affecting the membranes lining the lungs or abdomen, and linked to a poor survival, about 12 months after diagnosis.)

It turned out that fractal dimension and lacunarity measurements could easily distinguish cells of different histological types of mesothelioma, and also identify differences between benign and malignant tumors, and between non-tumor mesothelium and cancerous cells.

The study, published in the journal Scientific Reports, also demonstrated that the fractal and lacunarity properties of mitochondria could be used to classify various appearances, which correlated with the sensitivity of the mitochondria to mitochondrial blockers, such as metformin and Mdivi-1. Importantly, mitochondria from normal mesothelium were not sensitive to these drugs.

The findings were supported by traditional molecular analyses, showing altered expression of proteins in the mitochondria derived from different mesothelioma cells. These differences were also mirrored by changes in the bioenergetic profiles of the mitochondria, showing further proof of mitochondrial alterations in mesothelioma.

Since the classification of mitochondria using fractal properties and lacunarity is a rapid, robust, and objective assessment method, the authors suggested the method could be used to identify susceptible cell types in future treatment efforts targeting mitochondria in this devastating cancer.