Metastasis, the spread of cancer throughout the body, can be explained by the
fusion of a cancer cell with a white blood cell in the original tumor, according
to Yale School of Medicine researchers, who say that this single event can set
the stage for cancer’s migration to other parts of the body. — By Karen Peart
T H I S
Their work was published in the May issue of Nature Reviews Cancer.
The studies, spanning 15 years, have revealed that the newly formed hybrid of
the cancer cell and white blood cell adapts the white blood cell’s natural
ability to migrate around the body, while going through the uncontrolled cell
division of the original cancer cell. This causes a metastatic cell to emerge,
which like a white blood cell, can migrate through tissue, enter the circulatory
system and travel to other organs.
“This is a unifying explanation for metastasis,” says John Pawelek,
a researcher in the Department of Dermatology at Yale School of Medicine and
at Yale Cancer Center, who conducted the studies with Ashok K. Chakraborty, research
scientist in dermatology, and several other Yale colleagues. “Although
we know a vast amount about cancer, how a cancer cell becomes metastatic still
remains a mystery.”
The fusion theory was first proposed in the early 1900s and has attracted a lot
of scientific interest over the years. Pawelek and his colleagues began their
research several years ago by fusing white blood cells with tumor cells. These
experimental hybrids, the researchers observed, were remarkably metastatic and
lethal when implanted into mice. In addition, the scientists noted, some of the
molecules the hybrids used to metastasize originated from white blood cells,
and these molecules were the same as those used by metastatic cells in human
cancers. Pawelek and his team then validated previous findings that hybridization
occurs naturally in mice, and results in metastatic cancer.
“Viewing the fusion of a cancer cell and a white blood cell as the initiating
event for metastasis suggests that metastasis is virtually another disease imposed
on the pre-existing cancer cell,” says Pawelek. “We expect this to
open new areas for therapy based on the fusion process itself.”
The research team recently began studying cancers from individuals who had received
a bone marrow transplant — a new source of white blood cells for the patient.
Genes from the transplanted white blood cells were found in the patient tumor
cells, indicating that fusion with white blood cells had occurred. But Pawelek
said these studies must be greatly expanded before his team can say with certainty
that white blood cell fusion accounts for cancer metastasis in humans.
“To date, the fusion theory and the considerable evidence supporting it
have largely been overlooked by the cancer research community,” says Pawelek. “The
motivation for our article is to encourage other laboratories to join in.”
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IN MEMORIAM
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Let the sun shine
Campus Notes
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