Pancreatic cancer is very aggressive. This type of cancer often takes its victims within five years after diagnosis. Among the several forms of pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC) is the most common. Multiple factors can help explain the poor prognosis seen in patients with pancreatic cancer. First, pancreatic cancer grows fast. Second, the symptoms don't show up until late stages. This hinders the diagnosis and treatment of the disease. Third, current treatments are not effective enough.
Accumulating evidence suggests that the "wound"-like tissue that surrounds pancreatic tumors, called stroma, is much more dense than normal. The stroma appears to prevent cancer-killing drugs from reaching the tumor. Besides, the stroma appears to contain factors that facilitate tumor survival and growth. Based on these observations, some scientists hypothesize that destroying cells in the stroma could provide therapeutic effects against pancreatic cancer. However, elimination of cancer-associated fibroblasts (CAFs), the most common cell type in the stroma, actually make cancer more aggressive. It is possible that some of the cells destroyed could possess tumor-suppressive effects.
A team, composed of researchers from Centro Nacional de Investigaciones Oncológicas (CNIO), Columbia University Medical Center, German Cancer Research Center (DKFZ), Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM), Autonomous University of Madrid, and Murcian Institute of Biomedical Investigation (IMIB), recently carried out experiments to identify cells in the stroma that aid tumor growth.
Analyzing CAFs from mouse PDAC tumors and fibroblasts of normal pancreatic fibroblasts, the team discovered that a gene called Saa3
is a key mediator of the protumorigenic activity of CAFs. Saa3-expressing Saa3 stimulated tumor growth, while CAFs lacking Saa3 appeared to inhibit tumor growth. Further, The protumorigenic activity of Saa3 in CAFs is associated with another protein called Mpp6
. Analyzing samples from pancreatic cancer patients, the team discovered that SAA1, the ortholog of murine Saa3, is overexpressed in human CAFs, and this overexpression is associated with worse survival.
These data, collectively, show that SAA1 may play a key role on the protumorigenic properties of the stroma and in the progression of pancreatic cancer. Therefore, inhibiting SAA1 in CAFs may be a way to treat the devastating disease. The researchers hope to combine SAA1 inhibition with other therapeutic strategies in order to improve the treatment of patients with pancreatic cancer.
Findings of the study have been reported in a paper titled "Saa3 is a key mediator of the protumorigenic properties of cancer-associated fibroblasts in pancreatic tumors," appearing in the proceedings of the National Academy of sciences. Magdolna Djurec is the first author.
In humans, the SAA1 gene produces a protein that is also called SAA1 (Serum amyloid A1) whose biological function has not been fully understood. However, it is believed that increased blood level of SAA1 is related to many inflammatory conditions. Some studies support a link between SAA1 and tumor pathogenesis, and SAA1 contributes to tumor cell metastasis. To conclude, more research is needed to investigate the role of SAA1 in cancers like pancreatic cancer.