I know I just published my review of Cancer as a Metabolic Disease, but I stumbled across some news that I thought was worth relating.
One of the most beautifully written and compelling parts of Seyfried’s exhaustive hypothesis is the idea that metastasis is too complex of a process to be accounted for by random genetic mutation. The idea that many different types of cancer cells would all somehow collect the right genetic mutations that would make them able to enter and exit tissues, evade detection by the immune system, and spread throughout the body seems ludicrous. From the very beginnings of Cancer as a Metabolic Disease, Seyfried begins to question this and show how the process of metastasis involves abilities already present in some macrophages and leukocytes:
Moreover, we found that many metastatic cancers share multiple properties with cells of the myeloid origin (17). these are cells of the immune system such as macrophages and leukocytes. Macrophages and leukocytes are already mesenchymal cells genetically programmed to enter and exit tissues and to survive in hypoxic environments. These are hallmarks of most metastatic tumor cells. (45)
This is a recurring theme in the book, and at points he even notes that “Aichel proposed nearly a century ago that tumor progression involved fusion between leukocytes and somatic cells” (221). And it is this fusion-theory and not genetic mutation that Seyfried advocates as the source for a cancer cell’s ability to metastasize.
So it was with some satisfaction that I read this headline last night: Cancer Scientists Prove Long-Standing Theory on How Cancer Spreads:
“Our results provide the first proof in humans of a theory, proposed in 1911 by a German pathologist, that metastasis can occur when a leukocyte and cancer cell fuse and form a genetic hybrid,” said corresponding author John Pawelek, research faculty in the dermatology department of the Yale School of Medicine. “This could open the way to new therapy targets, but much work needs to be done to determine how fusion occurs, the frequency of such hybrids in human cancers, and the potential role of hybrids in metastasis,” he added.
From the research:
A model for metastasis resulting from fusion of bone marrow-derived cells is diagramed schematically in Figure 5. While this has largely been verified in animal tumor models and cell culture, evidence for fusion in human cancer has heretofore been lacking. Our findings show for the first time in a human cancer that generation of a metastasis and acquisition of its aberrant genetic patterns resulted from fusion and genomic hybridization between a BMDC and a cancer cell. Depending on the frequency of such events, the findings could have important implications for understanding metastasis, including the origins of tumor initiating cells and the cancer epigenome.
In other words, fusion and NOT genetic mutation account for metastasis.
And here is Seyfried:
In contrast to the EMT/MET explanation of metastasis, the macrophage cell fusion explanation of metastasis does not require the induction and reversion of extremely complicated gene regulatory systems. It is only a matter of time before the myeloid fusion hypothesis becomes the dominant explanation of cancer metastasis. (233)
Given the recent research, perhaps the time is nigh.
- A Melanoma Brain Metastasis with a Donor-Patient Hybrid Genome following Bone Marrow Transplantation: First Evidence for Fusion in Human Cancer, Lazova, LaBerge et al. PLOS One, June 26, 2013.
- Cancer as a Metabolic Disease, Thomas Seyfried.
- Cancer Scientists Prove Long-Standing Theory on How Cancer Spreads, SciTechDaily, June 28.