The novel focal adhesion gene kindlin-2 promotes the invasion of gastric cancer cells mediated by tumor-associated macrophages

Shen,Zhanlong; Ye,Yingjiang; Kauttu,Tuuli; Seppänen,Hanna; Vainionpää,Sanna; Wang,Shan; Mustonen,Harri; Puolakkainen,Pauli

doi:10.3892/or.2012.2137

The novel focal adhesion gene kindlin-2 promotes the invasion of gastric cancer cells mediated by tumor-associated macrophages

Authors:
- Zhanlong Shen
- Yingjiang Ye
- Tuuli Kauttu
- Hanna Seppänen
- Sanna Vainionpää
- Shan Wang
- Harri Mustonen
- Pauli Puolakkainen
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Affiliations: Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing 100044, P.R. China, Department of Surgery, Helsinki University Central Hospital, and University of Helsinki, Helsinki 00290, Finland
Published online on: November 14, 2012 https://doi.org/10.3892/or.2012.2137
Pages: 791-797

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Abstract

Kindlin-2 is a novel focal adhesion gene mediating the cell-extracellular matrix (ECM) adhesion. Tumor-associated macrophages (TAMs) play an important role in linking chronic inflammation to cancer progression. Both kindlin-2 and TAMs have been found to promote the invasion of gastric cancer cells in our previous studies. However, the correlation between kindlin-2 and TAMs remains unclear. Real-time RT-PCR was used to investigate kindlin-2 expression in the AGS, NCI and Hs-746T gastric cancer cell lines co-cultured with TAMs under normal or hypoxic conditions. IL8, IL10, IL11, IL17b, IL18, IL22 and IL24 expressions were measured by real-time RT-PCR in the gastric cancer lines with varying levels of kindlin-2 expression, as well as after downregulation of kindlin-2 mRNA expression by the siRNA method. We found that kindlin-2 was upregulated in all three gastric cancer cell lines when co-cultured with TAMs under normal conditions. Under hypoxic conditions, the induction of kindlin-2 expression induced by macrophages was significantly downregulated in the Hs-746T cell line. IL8, IL11, IL17b, IL22 and IL24 expression was significantly higher in gastric cell lines with high kindlin-2 expression. Downregulation of kindlin-2 mRNA decreased IL10, IL11, IL17b, IL22 and IL24 expression but IL8 and IL18 expression was upregulated. Therefore, the novel focal adhesion gene kindlin-2 may play an important role in promoting the invasion of gastric cancer cells mediated by TAMs through regulating interleukin expression.

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