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Interaction between adipose tissue stromal cells and gastric cancer cells in vitro

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Abstract

Adipose tissue exists in the gastric submucosa and subserosa. Thus, adipose tissue stromal cells (ATSCs), which include mesenchymal stem cells (MSCs), seem critical for the progression of gastric cancer but their interaction with the cancer cells is unknown. We demonstrated an interaction between these cells, using immunohistochemistry, Western blot and the collagen gel invasion assay system, in which the adenocarcinoma cells (well and poorly differentiated types, MKN28 and MKN45, respectively) were cultured on a ATSC-embedded or ATSC-non-embedded gel. ATSCs promoted the expression of the growth marker, proliferation cell nuclear antigen but inhibited that of the apoptosis marker, single-stranded DNA, in the cancer cell types. ATSCs accelerated the invasion of only MKN28 into the gel and promoted the expression of mitogen-activated protein kinase (MAPK, pERK-1/2) but decreased that of the molecularly targeted protein, HER2, in the cancer cells. ATSCs did not affect the expression of the prostaglandin biosynthetic enzyme cyclooxgenase-2 (COX-2) in the cancer cells. The COX-2 inhibitor celecoxib did not affect the morphology or invasion of the cancer cells. The cancer cell types in turn promoted the display of the myofibroblast marker, α-smooth muscle actin, whereas they decreased that of some MSC markers, e.g., CD44 and CD105, in ATSCs. The data suggest that (1) ATSCs influence the progression of gastric cancer by increasing their growth/invasion and decreasing their apoptosis through MAPK activation in a COX-2-independent way; (2) ATSCs adversely affect HER2-targeted therapy; (3) the cancer cells induce the cancer-associated myofibroblast phenotype in ATSCs.

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Acknowledgements

We thank Messrs. H. Ideguchi, S. Nakahara and F. Mutoh and Mrs. M. Nishida for their helpful technical assistance.

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Authors and Affiliations

  1. Department of Pathology & Microbiology, Faculty of Medicine, Saga University, Nabeshima 5-1-1, Saga, 8498501, Japan

    Namie Nomoto-Kojima, Shigehisa Aoki, Kazuyoshi Uchihashi, Aki Matsunobu & Shuji Toda

  2. Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, 8498501, Japan

    Namie Nomoto-Kojima, Akifumi Ootani & Kazuma Fujimoto

  3. Department of Health and Nutrition, Nagasaki International University, Nagasaki, Japan

    Namie Nomoto-Kojima

  4. Koike Hospital, Saga, 8400861, Japan

    Eisuke Koike

  5. Department of Pathology, Sasebo Chuo Hospital, Nagasaki, 8571195, Japan

    Nobuhisa Yonemitsu

Authors
  1. Namie Nomoto-Kojima
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  2. Shigehisa Aoki
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  3. Kazuyoshi Uchihashi
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  4. Aki Matsunobu
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  5. Eisuke Koike
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  6. Akifumi Ootani
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  7. Nobuhisa Yonemitsu
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  8. Kazuma Fujimoto
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  9. Shuji Toda
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Corresponding authors

Correspondence to Namie Nomoto-Kojima or Shuji Toda.

Additional information

This work was supported by Grants-in-Aid from the Japanese Ministry of Education, Culture, Sports, Science, and Technology for Scientific Research (nos. 18591871, 20592023 to S.T.; 20590728 to K.F.) and personal grants from Koike Hospital, Sasebo Chuo Hospital, Nagasaki Rosai Hospital and Yamada Clinic (to S.T.).

The authors declare no conflict of interest.

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Nomoto-Kojima, N., Aoki, S., Uchihashi, K. et al. Interaction between adipose tissue stromal cells and gastric cancer cells in vitro. Cell Tissue Res 344, 287–298 (2011). https://doi.org/10.1007/s00441-011-1144-3

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