Dartmouth Medical School researcher Murray Korc and German researchers Andrea Formentini and Olga Prokopchuk of the University of Ulm discovered that Interleukin-13, an anti-inflammatory cytokine, exerts autocrine growth-promoting effects on human pancreatic cancer and seems to facilitate lymph node metastases (spreading of cancer cells). The finding was published this month in International Journal of Colorectal Disease.
Interleukin-13 is a secreted immunomodulatory anti-inflammatory cytokine (regulatory protein released by immune system) produced in cells of hematopoietic origin (giving rise to blood cells). IL-13 was originally discovered in activated Th-2 lymphocytes (T helper cells) and has some activities with IL-4R (IL-13’s transmembrane receptor), though its potential in pancreatic ductal adenocarcinoma (PDAC) was not known.
According to the article, the research goal was to determine the role of IL-13 in PDAC and “whether pancreatic cancer cells produce IL-13 or whether IL-13 can modulate pancreatic cancer cell growth and influence the frequency of lymph node metastases.” The study suggests the latter.
The research team found that IL-13 enhanced the growth of ASPC-1, CAPAN-1 and COLO-357 cells, which are types of human pancreatic cancer cells. This cancer cell growth was associated with the activation of p44/42 mitogen-activated protein kinase (MAPK), a key component in the signal transduction of numerous mitogenic (inducing mitosis) growth factors. Neutralizing IL-13 antibodies inhibited the growth of ASPC-1 and CAPAN-1 cells.
While 30 of 70 PDAC samples revealed high levels of IL-13, over 94 percent of the samples exhibiting both high IL-13 and IL-4R had lymph node metastases. This suggests that IL-13, in addition to promoting pancreatic cancer cell proliferation in the presence of IL-4, may contribute to the inhibition of the immune system directed against pancreatic cancer, thereby facilitating tumor spread.
The study thus suggests that IL-13 has the potential to exert autocrine growth stimulatory effects in some pancreatic cell lines. The first evidence came from the fact that IL-13 stimulated pancreatic cancer cell growth. Second, pancreatic cancer cells expressed IL-13 at the mRNA and protein level and released IL-13 into medium. Third, anti-IL-13-neutralizing antibodies partially inhibited the growth of two out of three cell lines that were growth-stimulated by exogenous (external) IL-13. These results imply that IL-13 may enhance the growth of pancreatic cancer cells in vivo (within the living organism).
With the potential autocrine growth-promoting role of IL-13 in pancreatic cancer cells and its role in immunomodulation, it is possible that disruptions to this autocrine loop may have a therapeutic potential in the deadly pancreatic cancer in the future.
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