At Children’s Hospital Boston researchers crossed a couple pigment-lacking zebrafishes to produce one that is essentially transparent. Such a fish is thought to become a useful animal model that would allow direct observation of the growth of tumors.
White’s first experiment on the zebrafish examined how a cancer spreads. “The process by which a tumor goes from being localized to widespread and ultimately fatal is the most vexing problem that oncologists face,” says White. “We don’t know why cancer cells decide to move away from their primary site to other parts in the body.”
White created a fluorescent melanoma tumor in the transparent fish’s abdominal cavity. Viewing the fish under a microscope, White saw the cancer cells begin to spread within five days. He even saw individual cells metastasize, something that has not been observed, so readily and in real-time, in a living organism.
The spreading melanoma cells appeared to “home” to the skin after leaving the abdominal cavity. “This told us that when tumor cells spread to other parts in the body, they don’t do it randomly,” says White. “They know where to go.”
White plans to study tumor cell homing, then look for ways to modify the tumor cells or cells of the host so that the spreading cells never find their new location.
The fish may also answer questions about stem cell transplants. While transplants of blood-forming stem cells help cancer patients rebuild healthy blood, some transplants don’t “take,” for reasons that are unknown. Scientists have lacked a full understanding what steps blood stem cells must take to do their job, says White. White showed the process is observable in the fish. He first irradiated a transparent fish’s bone marrow, then transplanted fluorescent blood-forming stem cells from another zebrafish. By four weeks, the fluorescent stem cells had visibly migrated and grown in the fish’s bone marrow, which is in the kidney. Even individual stem cells were visible, something researchers haven’t easily observed in a living organism, White says.