Palladin, the travels continue

Our second Hard Science blogpost “Have Palladin, Will Travel,” on January 19, 2009, introduced the work of UNC cell and molecular physiologist Carol Otey and the protein she discovered a decade or so ago that plays an important role in cell motility, adhesion and structure.

Study first author Silvia Goicoechea, PhD and, on the right, Carol Otey, PhD in the Otey Lab at UNC

Also mentioned was Otey’s most recent work in which  palladin was found mutated in an inherited form of pancreas cancer and was also produced in large amounts — “upregulated” — in a number of sporadic pancreas tumors.

Now it appears that the protein with the fancy name may prove to be a molecular marker of pancreatic cancer , one that might help spot the disease at its earliest stages, when it can be treated more successfully with surgery.

In a finding published April 26, 2010, in the online journal PLoS One, the researcher and her colleagues  showed that a specific form of a protein called palladin is produced in large amounts in the “tumor nest,” the cells that surround a pancreatic tumor. 

The blue cells in the middle, surrounding the “space” in the center of a pancreatic duct, are the tumor cells, and the brown cells around them are the tumor-associated fibroblasts (stained for palladin).

Measuring the levels of this form of palladin in patient samples could provide an improved way to screen for the deadly cancer, possibly catching it earlier than ever before, said senior study author Carol Otey, Ph.D., associate professor of cell and molecular physiology at UNC.

“The problem with pancreas cancer is it is almost never caught at an early stage,” said Otey. “By the time a person develops suspicious symptoms, the disease has typically progressed too far. But if you can diagnose it early, it can be treated very effectively with surgery.” 

Otey and her colleagues decided to see if the upregulation of palladin in the tumor nest could provide a useful diagnostic tool for identifying the disease at earlier stages. They knew that the single palladin gene message can actually be cut and pasted together in a manner that produces at least seven different palladin protein products. Turns out only a couple of these forms of palladin – called isoforms – appear in pancreatic tissue. 

The researchers found that the longer of these two isoforms was upregulated in the cells surrounding the tumor — called tumor-associated fibroblasts — when compared to normal pancreas. Their findings were consistent, regardless of whether they were looking in cultured cell lines, patient samples, or tumors from a mouse model. 

Otey thinks that the upregulation of this form of palladin in tumor-associated fibroblasts could help them become contractile and stiff — more like muscle than connective tissue — in order to generate channels through neighboring tissue so the cancer can metastasize and spread.  

“The interactions between these tumor-associated fibroblasts and tumor cells are really important and are probably what is causing pancreas cancer to be so deadly,invasive and resistant to current therapies,” said Otey.

And that is why raising public awareness and enhancing our abilities to diagnose the disease early is so critical, says Hong Jin Kim, associate professor of surgery at UNC, who along with Otey is senior author of the study.

“It appears that the upregulation of palladin in the tumor-associated fibroblasts is an early event in the neoplastic process,” said Kim. “We may be able to take advantage of these findings, since pathologic confirmation of pancreatic adenocarcinoma in the preoperative setting is often difficult, requiring an invasive procedure directed by endoscopic ultrasound.  If we can enhance the diagnostic efficiency of these studies by staining for palladin, it would be clinically helpful for interventional gastroenterologists and pathologists.”

For palladin, the travels continue….

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