A Yale School of Medicine study in the December issue of Lancet Oncology challenges mainstream oncology researchers to consider tumor cell hybridization with white blood cells as a major reason that cancer metastasizes or spreads to other parts of the body.
"Cancer cells exhibit a remarkable number of traits normally attributed to white blood cells known as macrophages, including the ability to migrate to lymph nodes and distant organs and to form a new blood supply. Our data indicate that they do this by hybridizing with macrophages," said lead author John Pawelek, research affiliate in the Department of Dermatology at Yale School of Medicine and a member of Yale Cancer Center.
Pawelek said the idea of white blood cells hybridizing with tumor cells is not new. In the early 1900's the German pathologist Otto Aichel proposed that metastasis is caused by cancer cells fusing with macrophages. "There is now evidence to support all aspects of his proposition," said Pawelek. "Macrophages are among the most motile cells we have. By co-opting the macrophage's ability to move, the hybrid is very different from the original cancer cell. It is able to migrate away from the primary site of tumor formation and take up residence in other areas of the body while it continues to divide."
Working for more than a decade with a diverse team of scientists at the Yale School of Medicine and other research centers, Pawelek concludes that there is now sufficient evidence for Aichel's proposal to be taken seriously by the research community. Pawelek's group began testing the theory in 1993, when they created hybrids in the lab by fusing mouse melanoma cells with mouse macrophages.
"Their behavior was astonishing," said Pawelek. "In culture dishes, fused cells were extraordinarily motile compared to unfused melanoma cells. They spread rapidly when implanted in mice. Even though the idea is virtually unknown to cancer researchers today, many scientists worked on it in the 20th century. From the late 1960's up to today there have been many reports of tumor hybrids."
"Aichel implored future scientists to study cancer cells 'from all angles' for evidence of hybridization," Pawelek added. "It is remarkable that a century later we are doing just that. Were he alive today, Aichel would likely be both surprised and gratified, even though it might seem to be taking a rather long time."
Other researchers on the study were Douglas Brash, Ashok Chakraborty, Dennis Cooper, M.D., Tamara Handerson, M.D., Vincent Klump, Rossitza Lazova, M.D., James Platt, Stefano Sodi and Yesim Yilmaz, M.D.
Citation: The Lancet Oncology, Vol. 6, 12 (December 2005).
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