title: Interleukin-13 exerts autocrine growth-promoting effects on human pancreatic cancer, and its expression correlates with a propensity for lymph node metastases.
abstract: OBJECTIVE
  Interleukin-13 (IL-13) is an anti-inflammatory cytokine produced in cells of hematopoetic origin. It is not known 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.
  
  
  METHODS
  Cell growth and signaling were analyzed by cell counting, colorimetric proliferation assays, fluorescent-activated cell sorting, and in vitro kinase activity assays. IL-13 expression and secretion were determined by Northern blot analysis and enzyme-linked immunosorbent assay, respectively. Localization of IL-13 and its transmembrane receptor (IL-4R) in primary pancreatic ductal adenocarcinoma (PDAC) was characterized by immunohistochemistry.
  
  
  RESULTS
  IL-13 enhanced the growth of ASPC-1, CAPAN-1, and COLO-357 cells. This was associated with enhanced p44/42 mitogen-activated protein kinase (MAPK) phoshorylation. In contrast to p44/42 MAPK, phosphatidylinositol 3-kinase activity was also induced in IL-13-unresponsive MIA PaCa-2, PANC-1, and T3M4 cells. All cells expressed and secreted IL-13. Neutralizing IL-13 antibodies inhibited the growth of ASPC-1 and CAPAN-1 cells. Immunohistochemical analysis of resected primary ductal adenocarcinoma specimens revealed high levels of IL-13 in 30 of 70 cases and its transmembrane receptor (IL-4R) in 28 of 70 cases, respectively. Fifteen of 16 specimens (94%) exhibiting high IL-13 and IL-4R coexpression had lymph node metastases, while only 30 of the remaining 54 samples (56%) had positive lymph nodes (p = 0.0134).
  
  
  CONCLUSIONS
  IL-13 can act as an autocrine growth factor in PDAC. Endogenous expression of IL-13 in conjunction with IL-4R in the cancer cells seems to facilitate lymph node metastasis.
authors.affiliation: Clinic of General, Visceral, and Transplantation Surgery, University of Ulm, Steinhoevelstrasse 9, 89075, Ulm, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Formentini
authors.forename: Olga
authors.initials: O
authors.lastname: Prokopchuk
authors.forename: Joern
authors.initials: J
authors.lastname: Sträter
authors.forename: Joerg
authors.initials: J
authors.lastname: Kleeff
authors.forename: Lukasz Filip
authors.initials: LF
authors.lastname: Grochola
authors.forename: Gerd
authors.initials: G
authors.lastname: Leder
authors.forename: Doris
authors.initials: D
authors.lastname: Henne-Bruns
authors.forename: Murray
authors.initials: M
authors.lastname: Korc
authors.forename: Marko
authors.initials: M
authors.lastname: Kornmann