In the beginning  pg. 4

Cell migration

Gastrulation is a time in early development when an initially amorphous ball of cells begins taking on its adult shape due to rapid and extensive cell movements. Metastasis also is characterized by cell movements—cancer cells break off the primary tumor and spread throughout the body.

“My main interest is trying to understand the fundamental migratory differences between metastatic (invasive) tumor cells and primary (non-invasive) tumors,” Jessen says. He is currently searching for molecular signals in the Wnt pathway that might underlie cell motility during both metastasis and zebrafish gastrulation.

A major goal of the Jessen lab is to develop a model of melanoma, a deadly form of skin cancer, by transplanting human melanoma cells into zebrafish embryos. The idea of using the zebrafish embryo to model a disease that afflicts humans is very exciting, Jessen explains.

“We can manipulate the embryonic environment to determine what kind of environmental cues (such as the Wnt pathway) might influence tumor cell migration.”

An added benefit of zebrafish cancer models is the ease and cost-effectiveness of doing in vivo drug screens.

“What’s interesting is that fish tumors look very similar to human tumors,” Jessen says. “And you can bathe (zebrafish embryos) in chemicals and look for molecules that inhibit or promote growth of the tumor.”

Jessen is also combining developmental biology and cancer research through a more traditional approach, using the zebrafish embryo to determine how proteins associated with cancer and metastasis regulate cell migration normally, such as during gastrulation.

“It is important to remember that for the majority of cancer proteins, we know very little about how these proteins function to control basic cellular activities such as motility,” Jessen says.

While both cancer and development are exceedingly complex processes, insights about developmental pathways like Wnt are slowly beginning to reveal the genetic underpinnings of tumorigenesis.

“It’s so complex that no one lab or company is going to come up with the answer to cancer,” says Jessen. “I see myself as trying to fill in some of the key gaps in our knowledge.”

Another pathway involved in both embryonic development and cancer is the “Hedgehog” (Hh) pathway. First identified in fruit flies, it is named for the “short and prickly” appearance of fly embryos that have an abnormal Hh protein due to a genetic mutation.

Like Wnt, Hh is a secreted signaling molecule involved in the patterning of the embryo. Also like Wnt, Hh appears linked to the formation of tumors in those tissues where it is required for development—the cerebellum, foregut, prostate, skin and lung, for example.

In some cases, the Hh protein “may tell some cells to proliferate,” says Michael Cooper, M.D., an assistant professor of Neurology at Vanderbilt. In other cases, “it may tell cells to differentiate along a certain lineage… to become a motor neuron,” for example.

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