Researchers at the Kimmel Cancer Center at Jefferson haveidentified cancer cell mitochondria as the unsuspecting powerhouse and “Achilles’heel” of tumor growth, opening up the door for new therapeutictargets in breast cancer and other tumor types. Reporting in the online Dec.1 issue of Cell Cycle, Michael P.Lisanti, M.D., Ph.D., Professor and Chair of Stem Cell Biology &Regenerative Medicine at Thomas Jefferson University, andcolleagues provide the first in vivo evidence that breast cancercells perform enhanced mitochondrial oxidative phosphorylation(OXPHOS) to produce high amounts of energy. “We and others have now shown that cancer is a ‘parasitic disease’that steals energy from the host — your body,” Dr. Lisanti said,”but this is the first time we’ve shown in human breast tissue thatcancer cell mitochondria are calling the shots and could ultimatelybe manipulated in our favor.” Mitochondria are the energy-producing power-plants in normal cells.However, cancer cells have amplified this energy-producingmechanism, with at least five times as much energy-producingcapacity, compared with normal cells.
Simply put, mitochondria arethe powerhouse of cancer cells and they fuel tumor growth andmetastasis. The research presented in the study further supports the idea thatblocking this activity with a mitochondrial inhibitor — forinstance, an off-patent generic drug used to treat diabetes known as Metformin — can reverse tumor growth and chemotherapyresistance. This new concept could radically change how we treatcancer patients, and stimulate new metabolic strategies for cancerprevention and therapy. Investigating the Powerhouse Whether cancer cells have functional mitochondria has been a hotlydebated topic for the past 85 years. It was argued that cancercells don’t use mitochondria, but instead use glycolysisexclusively; this is known as the Warburg Effect.
But researchersat the Jefferson’s KCC have shown that this inefficient method ofproducing energy actually takes place in the surrounding hoststromal cells, rather then in epithelial cancer cells. This processthen provides abundant mitochondrial fuel for cancer cells. They’vecoined this the “Reverse Warburg Effect,” the opposite or reverseof the existing paradigm. To study mitochondria’s role directly, the researchers, includingco-author and collaborator Federica Sotgia, Assistant Professor inthe Department of Cancer Biology, looked at mitochondrial functionusing COX activity staining in human breast cancer samples.Previously, this simple stain was only applied to muscle tissue, amitochondrial-rich tissue. Coffee Packaging Bags
Researchers found that human breast cancer epithelial cells showedamplified levels of mitochondrial activity. In contrast, adjacentstromal tissues showed little or no mitochondrial oxidativecapacity, consistent with the new paradigm. These findings werefurther validated using a computer-based informatics approach withgene profiles from over 2,000 human breast cancer samples. It is now clear that cancer cell mitochondria play a key role in”parasitic” energy transfer between normal fibroblasts and cancercells, fueling tumor growth and metastasis. Coffee Packaging Bags Manufacturer
“We have presented new evidence that cancer cell mitochondria areat the heart of tumor cell growth and metastasis,” Dr. Lisantisaid. “Metabolically, the drug Metformin prevents cancer cells fromusing their mitochondria, induces glycolysis and lactateproduction, and shifts cancer cells toward the conventional’Warburg Effect’. This effectively starves the cancer cells todeath”. Vacuum Seal Food Bags Manufacturer
Personalized Treatment Although COX mitochondrial activity staining had never beenapplied to cancer tissues, it could now be used routinely todistinguish cancer cells from normal cells, and to establishnegative margins during cancer surgery. And this is a verycost-effective test, since it has been used routinely formuscle-tissue for over 50 years, but not for cancer diagnosis. What’s more, it appears that upregulation of mitochondrial activityis a common feature of human breast cancer cells, and is associatedwith both estrogen receptor positive (ER+) and negative (ER-)disease. Outcome analysis indicated that this mitochondrial genesignature is also associated with an increased risk of tumor cellmetastasis, particularly in ER-negative (ER-) patients. “Mitochondria are the ‘Achilles’ heel’ of tumor cells,” Dr.
Lisantisaid. “And we believe that targeting mitochondrial metabolism hasbroad implications for both cancer diagnostics and therapeutics,and could be exploited in the pursuit of personalized cancermedicine.” Additional References Citations.