Identification of Key Protein Prevents Pancreatic Cancer Growth in Mice

A research team at Stanford University has discovered a protein critical for the growth of pancreatic cancer tumors that, when expression was blocked, prevented tumor growth in mice.

The researchers studied connective tissue growth factor (CCN2), a protein that is involved in the abnormal growth of connective tissue when faced with injury or disease. It had been hypothesized that CCN2 was also involved in the progression of pancreatic tumors, although its exact role was previously unknown. Cancer biologist Amato Giaccia, PhD, senior author of the study, and his collaborators discovered that human pancreatic cancer cells expressing high levels of CCN2 grew rapidly when injected under the skin of mice. Tumors with CCN2 cells out-competed others that were expressing lower levels of the protein. In the pancreatic cancer cells where CCN2 expression was limited, tumors were less likely or even unable to form.

CCN2 cancer cells were also directly injected into the animals’ pancreases, where highly expressed levels of the protein led to larger tumors that metastasized more aggressively, compared to those expressing low levels. The mice that were injected with cancer cells expressing high levels of CCN2 also died sooner.

“This research clearly shows that inhibiting the protein inhibits the tumor’s ability to grow,” Giaccia said.

The research team also found that blocking CCN2 expression in cultured pancreatic cells made the cells much more sensitive to hypoxia-induced death. CCN2 was present in higher levels in pancreatic tumor samples than in neighboring tissues, and hypoxic conditions actually led to the creation of CCN2 by the pancreatic cancer cells.

The team is hoping to explore whether or not people with pancreatic cancer could benefit from therapies that target CCN2. A phase-I clinical trial that is testing the safety of an antibody that binds CCN2 and blocks its activity began in December at Stanford and Dartmouth-Hitchcock Medical Center with a small number of patients.

“We saw a pronounced effect of CCN2 inhibition in these experiments in mice,” Giaccia said. “Our hope is that one day a combination of standard therapy and antibody treatment will have an effect on tumor progression in human patients.”

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specialty: oncology