CCL20 derived from PMA-differentiated macrophages abrogates TGF-β1-induced expression of cancer progression suppressor CXCL14 in HSC-4 cells in PI3K-, MEK1/2-, and NF-κB-dependent manners

• TAKEDA Kei

  Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University Division of Oral and Maxillofacial Surgery, Department of Reconstructive Oral and Maxillofacial Surgery, Iwate Medical University School of Dentistry

• ISHIKAWA Yuudai

  Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University Division of Oral and Maxillofacial Surgery, Department of Reconstructive Oral and Maxillofacial Surgery, Iwate Medical University School of Dentistry

• KOMATSU Yuko

  Division of Oral and Maxillofacial Surgery, Department of Reconstructive Oral and Maxillofacial Surgery, Iwate Medical University School of Dentistry

• YAMADA Hiroyuki

  Division of Oral and Maxillofacial Surgery, Department of Reconstructive Oral and Maxillofacial Surgery, Iwate Medical University School of Dentistry

• ISHISAKI Akira

  Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University

• KAMO Masaharu

  Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University

Abstract

Squamous cell carcinoma（ SCC） is the most common cancer that develops in the oral cavity. Epithelial-mesenchymal transition（ EMT） is known to play an important role in the process of metastasis of SCC cells. In our previous study, we demonstrated that transforming growth factor-β1 （TGF-β1） induces EMT in the human oral SCC（ hOSCC） cell line HSC-4. However, the molecular mechanisms of the metastasis after an EMT-induced cancer are poorly understood. Moreover, tumorassociated macrophages（ TAMs）, which coexist with the cancer tissues, are known to participate in permeation metastasis. However, it still remains uncertain whether TAMs affect the metastatic activity of hOSCC cells. We found that the expression of CXCL14, which is known to suppress the progression of colon, and breast cancers, was upregulated in HSC-4 cells by TGF-β1 stimulation. The Smad3 inhibitor, SIS3, suppressed the TGF-β1-induced expression of CXCL14. Interestingly, the CXCL14 suppressed the migratory and proliferative activities in HSC-4 cells. Moreover, the expression of CXCL14 in HSC-4 cells was downregulated by cocultivation with differentiated macrophages derived from monocytic THP-1 cells, but not by cocultivation with non-differentiated monocytic THP-1 cells. On the other hand, we found that expression levels of CCL20 in the differentiated macrophages derived from THP-1 cells was higher than that in non-differentiated monocytic THP-1 cells. In addition, CCL20 suppressed TGF-β1-induced expression of CXCL14. Intriguingly, the MAPK/ERK kinase （MEK） inhibitor U0126, PI3K inhibitor LY294002, or NF-κB kinase-2（ IKK-2） inhibitor TPCA-1　abrogated the CCL20-promoted inhibition of TGF-β1-induced expression of CXCL14. Moreover, CCL20 decreased the migratory activity of HSC-4 cells. Taken together, these results suggest that CCL20 derived from TAMs abrogated the TGF-β1-induced expression of the cancer progression suppressor CXCL14 in HSC-4 cells in PI3K-, MEK1/2-, and NF- κB-dependent manners, resulting in the activation of metastatic activity in HSC-4 cells.

Journal

• Dental Journal of Iwate Medical University

  Dental Journal of Iwate Medical University 46 (1), 19-32, 2021-07-20

  The Dental Society of Iwate Medical University

Keywords

• CCL20
• CXCL14
• epithelial-mesenchymal transition
• squamous cell carcinoma
• transforming growth factor-β

Details

• CRID: 1390852252714752128
• NII Article ID: 130008084397
• DOI: 10.20663/iwateshigakukaishi.46.1_19
• ISSN: 24241822
• ISSN: 03851311
• Text Lang: en
• Data Source:
  • JaLC
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed