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. 2022 Jan;42(1):501-509.
doi: 10.21873/anticanres.15508.

Dipeptidyl Peptidase-4 from Cancer-associated Fibroblasts Stimulates the Proliferation of Scirrhous-type Gastric Cancer Cells

Shuhei Kushiyama  1   2   3 , Masakazu Yashiro  4   2   3 , Yurie Yamamoto  2   3 , Tomohiro Sera  1   2   3 , Atsushi Sugimoto  1   2   3 , Sadaaki Nishimura  1   2   3 , Shingo Togano  1   2   3 , Kenji Kuroda  1   2   3 , Tomohisa Okuno  1   2 , Yuichiro Miki  1   2 , Masaichi Ohira  1
Affiliations

Dipeptidyl Peptidase-4 from Cancer-associated Fibroblasts Stimulates the Proliferation of Scirrhous-type Gastric Cancer Cells

Shuhei Kushiyama et al. Anticancer Res. 2022 Jan.

Abstract

Background/aim: Cancer-associated fibroblasts (CAFs) may promote the malignancy of human scirrhous gastric cancer (SGC) cells. We conducted the present study to identify novel growth factors from CAFs.

Materials and methods: OCUM-12 and 2 CAF cell lines were used. The proliferation of cancer cells was determined by the number of cancer cells or the MTT assay. The growth factor(s) were purified and characterized by the gel filtration chromatography and protein array.

Results: The molecular weight of the growth-stimulating factor was estimated to be approximately 66-669 kDa. Protein array of conditioned medium (CM) from CAFs indicated that dipeptidyl peptidase-4 (DPP-4) was one of the growth factors. The addition of CM increased the phosphorylation of C-X-C chemokine receptor 4 (CXCR4). The DPP-4 inhibitor significantly inhibited the growth-stimulating activity of CM.

Conclusion: DPP-4 from CAFs might be one of the growth-stimulating factors for SGC through CXCR4.

Keywords: Cancer-associated fibroblasts; cancer microenvironment; dipeptidyl peptidase-4; proliferation; scirrhous-type gastric cancer.

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