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  • IL-22 produced by cancer-associated fibroblasts promotes gastric cancer cell invasion via STAT3 and ERK signaling.

IL-22 produced by cancer-associated fibroblasts promotes gastric cancer cell invasion via STAT3 and ERK signaling.

British journal of cancer (2014-06-18)
H Fukui, X Zhang, C Sun, K Hara, S Kikuchi, T Yamasaki, T Kondo, T Tomita, T Oshima, J Watari, J Imura, T Fujimori, M Sasako, H Miwa
ABSTRACT

Interleukin-22 (IL-22) has been recently highlighted owing to its biological significance in the modulation of tissue responses during inflammation. However, the role of IL-22 in carcinogenesis has remained unclear. Here, we investigated the pathophysiological significance of IL-22 expression in gastric cancer tissues and examined the mechanism by which IL-22 promotes gastric cancer cell invasion. Human gastric cancer specimens were analysed by immunohistochemistry for expression of IL-22 and IL-22 receptor 1 (IL-22R1). The effects of IL-22-induced STAT3 and ERK signalling on invasive ability of gastric cancer cells were examined using a small-interfering RNA system and specific inhibitors. AGS cells were co-cultured with cancer-associated fibroblasts (CAFs) from human gastric cancer tissues and assessed by invasion assay. Interleukin-22 and its receptor were expressed in α-smooth muscle actin-positive stromal cells and tumour cells at the invasive front of gastric cancer tissues, respectively. The expression of IL-22 and IL-22R1 was significantly related to lymphatic invasion. Interleukin-22 treatment promoted the invasive ability of gastric cancer cells through STAT3 and ERK activation. The invasive ability of gastric cancer cells was significantly enhanced by co-culture with IL-22-expressing CAFs. Interleukin-22 produced by CAFs promotes gastric cancer cell invasion via STAT3 and ERK signalling.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
IL-22 human, Animal-component free, recombinant, expressed in E. coli, ≥98% (SDS-PAGE), ≥98% (HPLC)
Sigma-Aldrich
IL-22 human, recombinant, expressed in E. coli, ≥98% (SDS-PAGE), ≥98% (HPLC), suitable for cell culture
Sigma-Aldrich
MISSION® esiRNA, targeting mouse Stat3
Sigma-Aldrich
Wortmannin, from Penicillium funiculosum, ≥98% (HPLC and TLC)
Sigma-Aldrich
MISSION® esiRNA, targeting human STAT3