Claudio Vinegoni, Ph.D. | Computational imaging reveals mitochondrial morphology as a biomarker of cancer phenotype and drug response

Sci. Rep.
Computational imaging reveals mitochondrial morphology as a biomarker of cancer phenotype and drug response

Giedt, R. J., Fumene Feruglio, P., Pathania, D., Yang, K. S., Kilcoyne, A., Vinegoni, C., Mitchison, T. J., and Weissleder^#, R.

Scientific Reports 2016

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Mitochondria, which are essential organelles in resting and replicating cells, can vary in number, mass and shape. Past research has primarily focused on short-term molecular mechanisms underlying fission/fusion. Less is known about longer-term mitochondrial behavior such as the overall makeup of cell populations’ morphological patterns and whether these patterns can be used as biomarkers of drug response in human cells. We developed an image-based analytical technique to phenotype mitochondrial morphology in different cancers, including cancer cell lines and patient-derived cancer cells. We demonstrate that (i) cancer cells of different origins, including patient-derived xenografts, express highly diverse mitochondrial phenotypes; (ii) a given phenotype is characteristic of a cell population and fairly constant over time; (iii) mitochondrial patterns correlate with cell metabolic measurements and (iv) therapeutic interventions can alter mitochondrial phenotypes in drug-sensitive cancers as measured in pre-versus post-treatment fine needle aspirates in mice. These observations shed light on the role of mitochondrial dynamics in the biology and drug response of cancer cells. On the basis of these findings, we propose that image-based mitochondrial phenotyping can provide biomarkers for assessing cancer phenotype and drug response.
@article{2016-SCIREP, author= {Giedt, R. J. and Fumene Feruglio, P. and Pathania, D. and Yang, K. S. and Kilcoyne, A. and Vinegoni, C. and Mitchison, T. J. and Weissleder<sup>#</sup>, R.}, title= {Computational imaging reveals mitochondrial morphology as a biomarker of cancer phenotype and drug response}, journal= {Scientific Reports}, alternatejournal = {Sci. Rep.}, year = {2016}, volume = {6}, pages = {10}, issn = {2045-2322}, doi = {10.1038/srep32985}, pmcid = {PMC5017129}, pmid= {27609668} }
27609668

PMC5017129

10.1038/srep32985

Abstract

"Mitochondria, which are essential organelles in resting and replicating cells, can vary in number, mass and shape. Past research has primarily focused on short-term molecular mechanisms underlying fission/fusion. Less is known about longer-term mitochondrial behavior such as the overall makeup of cell populations' morphological patterns and whether these patterns can be used as biomarkers of drug response in human cells. We developed an image-based analytical technique to phenotype mitochondrial morphology in different cancers, including cancer cell lines and patient-derived cancer cells. We demonstrate that (i) cancer cells of different origins, including patient-derived xenografts, express highly diverse mitochondrial phenotypes; (ii) a given phenotype is characteristic of a cell population and fairly constant over time; (iii) mitochondrial patterns correlate with cell metabolic measurements and (iv) therapeutic interventions can alter mitochondrial phenotypes in drug-sensitive cancers as measured in pre-versus post-treatment fine needle aspirates in mice. These observations shed light on the role of mitochondrial dynamics in the biology and drug response of cancer cells. On the basis of these findings, we propose that image-based mitochondrial phenotyping can provide biomarkers for assessing cancer phenotype and drug response."

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For attribution in academic contexts, please cite this work as:

Giedt, R. J., Fumene Feruglio, P., Pathania, D., Yang, K. S., Kilcoyne, A., Vinegoni, C., Mitchison, T. J., & Weissleder^#, R. (2016). Computational imaging reveals mitochondrial morphology as a biomarker of cancer phenotype and drug response. Scientific Reports, 6, 10. https://doi.org/10.1038/srep32985