New imaging technique could personalize cancer therapy

Researchers devise an innovative imaging technique to study an enzyme called tubulin tyrosine ligase, which can indicate how aggressive are person's cancer is and therefore how it should be treated.

Susannah Gal (left) and Susan Bane have devised a new imaging technique to view specific proteins in action. Jonathan Cohen

Two professors at Binghamton University in New York are using a novel imaging technique to observe the behavior of an enzyme--called tubulin tyrosine ligase, or TTL--as its behavior can suggest whether certain cancer cells might grow more aggressively than others.

Though they are not developing actual therapies, Susan Bane and Susannah Gal say their research could help further personalize targeted cancer therapies.

"Potentially, we could put [a tumor sample] in our labeling system and say, 'Yes, that has a problem with the TTL system, and therefore you should be more aggressive with it,'" says Gal, whose work is funded by the National Institute of General Medical Sciences. "Or we could say, 'That's probably OK, so you can treat it with normal chemotherapy.'"

The enzyme TTL involves microtubules, which both help chromosomes line up correctly during cell division and provide part of the scaffolding of a cell's structure. Those microtubules are made of proteins called tubulin; the enzyme carboxypeptidase clips an amino acid called tyrosine off the ends of some of these proteins, and later the enzyme TTL puts that tyrosine back on.

Bane says it's unclear why tyrosine is clipped off only to be reattached, but it's clearly an important part of the cell's cycle: "We do know that if you don't have that enzyme, you'll die."

In some cancer cells, that cycle of removing and reattaching tyrosine is disrupted, with too many tubulins lacking tyrosine altogether. Tumors made of those cells, Bane says, "tend to grow more aggressively."

Berkeley Lab published the first 3D model of tubulin in 1998. Berkeley Lab

Being able to watch this cycle, then, could provide profound insights into the nature of a particular person's cancer and how to treat it. But watching these microtubules divide is tricky; most fluorescent markers don't distinguish between tubulin and other protein molecules and will bond to any of them. Typically, markers that can distinguish between them are so big that they block the view of the protein being studied.

This is where their new imaging technique comes into play. To mark only tubulin, Bane and Gal dressed it in a "hat"--a special derivative of tyrosine that Bane created for the project--and then introduced a fluorescent molecule that lights up only when it bonds with that special tyrosine, allowing researchers to distinguish tubulin from other objects in the cell and watch how it behaves.

In 1998, after 30 years of work, scientists completed 3D imaging of the atomic structure of tubulin. Today, Bane and Gal hope that being able to watch tubulin in action might will provide significant insights into how to treat an individual's specific tumor more effectively.

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