Researchers at University of Texas M.D. Anderson Cancer Center and University of North Carolina at Chapel Hill collaborated on a study due to be published on the March 25 issue of Oncogene. The renowned researchers from the prestigious universities discovered a protein–palladin that plays an important role in the metastatic spread of pancreatic cancer.
The high metastatic potential of pancreatic cancer is attributed to the paladin induced stimulation of cancer associated fibroblast (CAF) to dissolute cellular barriers in order to promote the spread of cancer cells. This is achieved by assembling of CAFs with the help of invadopodia (that acts as a major contributing factor in the dissolution of cellular barriers with the help of physical force and enzymatic activity)
The researchers observed this effect by inoculating cancer cells in between the layers of collagen and recording the CAF activity. The cancer cells utilized the channels produced by invadopodia and metastasize from their primary location. Just as the fibroblasts are the most pre-dominant connective tissue component in normal organs, cancer associated fibroblasts are the most commonly occurring cells in the tumor environment. Researchers from Carol Otey’s lab, along with Rosa Hwang (a researcher from University of Texas M.D. Anderson Cancer Center) and other collaborators discovered that CAF in the vicinity of pancreatic cancer express palladin in substantially high levels.
As part of the research study, the Otey research team concluded that the use of certain silencing genes and palladin inhibitors can alter the ability of CAF to produce invadopodia that can directly affect the progression and spread of cancer cells; on the contrary, higher palladin levels are strongly associated with a higher expression of invadopodia and a higher metastatic potential of cancers.
“These results demonstrate that the behavior of CAFs plays a very important role in modulating the behavior of tumor cells, and also point to a specific molecular pathway that could be a useful drug target for inhibiting tumor progression”
Research conducted by Temple University’s Fox Chase Cancer Center also suggests that high palladin levels are associated with low survival rates in the renal carcinoma patients. Otey and her team will be working in future to examine the effect and role of palladin on other cancers.