Mitochondria in relation to cancer metastasis: Introduction to a mini-review series

Department of Biological Chemistry and Oncology, Sidney Kimmel Cancer Center, and Center for Metabolism and Obesity Research, School of Medicine, Johns Hopkins University, 735 North Wolfe Street, Baltimore, MD, 21205, USA, .
Journal of Bioenergetics (Impact Factor: 3.21). 08/2012; 44(6). DOI: 10.1007/s10863-012-9470-z
Source: PubMed


This introductory article and those that follow focus on the roles that mitochondria may have in cancer metastasis (spreading) that all too frequently leads to death of cancer patients. The history of cancer dates back in time to several thousand years BC and continues to this day. Although billions of dollars have been invested, numerous cancer researchers/scientists and oncologist located at universities, hospitals, cancer centers, commercial entities (companies), and government agencies have been unable to discover "magic bullets" to quickly silence most cancers. That is, agents that are effective not only in eradicating the primary tumor at its site of origin, but eradicating also distant tumors that have arisen therefrom via metastatic cells. Fortunately, in recent years some researchers have obtained evidence that the mitochondria of cancer cells are involved not only in providing in part the necessary energy (ATP) to fuel their growth, but hold the secrets to their immortality, and propensity to metastasize (spread) from their original site of origin to other body locations. This introductory article, as well as those that follow, focus on the possible roles of mitochondria in cancer metastasis as well as strategies to arrest cancer metastasis based on this knowledge. Ideally, for a patient to become "cancer free" the anticancer agent/agents used must 1) eradicate the primary tumor at its site of origin, 2) eradicate any tumors at other body locations that have arisen via metastasis, and 3) eradicate any tumor cells that remain in the blood, i.e., circulating tumor cells. One such agent that holds promise for doing all three is the small molecule 3-bromopyruvate (3BP) discovered in the author's laboratory by Dr. Young H. Ko near the turn of the century to be a potent anti-cancer agent [Ko et al.(2001) Can Lett 173:83-91].

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    ABSTRACT: Animal models for studying human disease are essential to the continuing evolution of medicine. Rodent models are attractive for the obvious similarities in development and genetic makeup compared with humans, but have cost and technical limitations. The zebrafish (Danio rerio) represents an excellent alternative vertebrate model of human disease because of its high conservation of genetic information and physiological processes, inexpensive maintenance, and optical clarity facilitating direct observation. This review highlights recent advances in understanding genetic disease states associated with the dynamic organelle, the mitochondrion, using zebrafish. Mitochondrial diseases that have been replicated in the zebrafish include those affecting the nervous and cardiovascular systems, as well as red blood cell function. There are a large number of studies involving genes associated with Parkinson's disease, as well as many of the genes associated with heme synthesis and anemia. Gene silencing techniques, including morpholino knockdown and TAL-effector endonucleases have been exploited to demonstrate how loss of function can induce human diseaselike states in zebrafish. Moreover, modeling mitochondrial diseases has been facilitated greatly by the creation of transgenic fish with fluorescently labeled mitochondria for in vivo visualization of these structures. In addition, behavioral assays have been developed to examine changes in motor activity and sensory responses, particularly in larval stages. Zebrafish are poised to advance our understanding of the pathogenesis of human mitochondrial diseases beyond the current state of knowledge and provide a key tool in the development of novel therapeutic approaches to treat these conditions.
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