Interleukin-13 exerts autocrine growth-promoting effects on human pancreatic cancer, and its expression correlates with a propensity for lymph node metastases

Andrea Formentini, Olga Prokopchuk, Joern Sträter, Joerg Kleeff, Lukasz Filip Grochola, Gerd Leder, Doris Henne-Bruns, Murray Korc, Marko Kornmann

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27 Scopus citations

Abstract

Background and aims: 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. Materials and 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). Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)57-67
Number of pages11
JournalInternational Journal of Colorectal Disease
Volume24
Issue number1
DOIs
StatePublished - Jan 1 2009

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Keywords

  • Cytokine
  • Growth factor
  • Interleukin
  • Metastatic spread
  • Pancreatic cancer

ASJC Scopus subject areas

  • Gastroenterology

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