CXCL14, a unique multistep tumor suppressing chemokine, regulates expression of cancer stem cell markers

• Project/Area Number: 17K17112
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Kanagawa Dental College
• Principal Investigator: Yang Xiaoyan 神奈川歯科大学, 大学院歯学研究科, 特別研究員 (90744954)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 多機能癌抑制分子 / 口腔癌 / ケモカインCXCL14 / 多段階癌抑制分子 / CXCL14 / 癌抑制分子 / ケモカイン

Outline of Final Research Achievements

Cancer is a leading cause of death and disease worldwide, with a tremendous financial impact. Thus, the development of cost-effective novel approaches for suppressing tumor growth and progression is essential. We previously reported that the chemokine CXCL14 is a multistep tumor suppressor that suppresses carcinogenesis, tumor growth and metastasis. In order to clarify molecular mechanisms of this unique tumor suppression mechanisms by CXCL14, we investigated effects of CXCL14 on the expression of cancer stem cell factors.
When cells were injected into back skin of nude mice,CXCL14 knockout(KO) cells produced much larger tumors compared with parental HSC-3 cells and representative cancer stem cell factors such as CD44v3, CD44v6 and CD44v9 were higher in KO cells compared with parental oral carcinoma cells. These lines of evidence suggest that CXCL14 regulates cancer stemness in oral carcinoma.

Academic Significance and Societal Importance of the Research Achievements

我々の結果は種々の癌に応用可能な普遍的な癌の抑制法の開発につながる可能性がある。癌幹細胞を標的とした普遍的な癌抑制機構については報告がない。CXCL14を用いた癌の治療法は個々の癌に対する対症療法でなく、自己の防御機構を高めるので、癌の予防に繋がり、将来、健康寿命の延長、医療費、介護費用の大幅な削減への道を拓く事が期待される。また、本研究結果により、将来、生体内の癌抑制機構の活性化による、副作用のない、種々の癌に適用可能な、患者に優しい、画期的な 癌抑制法や予防法開発ためのデーターを提供できる。

Research Products

• [Journal Article] C-X-C Motif Chemokine Ligand 14 is a Unique Multifunctional Regulator of Tumor Progression. International Journal of Molecular (2019)
  • Author(s): Xiao-Yan Yang,Shigeyuki Ozawa, Yasumasa Kato, Yojiro Maehata, Kazuhito Izukuri1, Takeharu Ikoma, Keisuke Kanamori, Tetsu Akasaka, Kenji Suzuki, Hiroshi Iwabuchi, Shun-Ichi Kurata, Iyoko Katoh,, Takashi Sakurai, Tohru Kiyono, Ryu-Ichiro Hata
  • Journal Title: International Journal of Molecular Sciences Volume: 20 Issue: 8 Pages: 1872-1872
  • DOI: 10.3390/ijms20081872
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] CXCL14, a unique multistep tumor suppressing chemokine, regulates expression of stem cell factors (2019)
  • Author(s): Ryu-Ichiro Hata, Xiaoyan Yang, Shigeyuki Ozawa, Kazuhito Izukuri1, Takeharu Ikoma, Keisuke Kanamori, Kenji Suzuki,Yojiro Maehata, Tohru Kiyono
  • Organizer: Bit’s World Cancer Congress-2019
• [Presentation] 口腔癌細胞において癌抑制性ケモカインCXCL14の発現は癌幹細胞マーカーの発現を制御する (2019)
  • Author(s): 畑隆一郎, 陽暁艶, 小澤重幸, 居作和人, 生駒丈晴, 金森慶亮, 鈴木健司, 前畑洋次郎, 服部俊治, 水野一乘, 清野透
  • Organizer: 第51回日本結合組織学会学術大会
• [Presentation] CXCL14, a multistep tumor suppressing chemokine, regulates expression of stem cell factors. (2018)
  • Author(s): Yang X-Y, Ozawa S, Ikoma T, Kanamori K, Suzuki K, Izukuri K, Maehata Y, Kiyono T, Hata R-I
  • Organizer: 第50回日本結合組織学会学術大会
• [Presentation] Chemokine CXCL14/BRAK transgenic mice suppress carcinogenesis, tumor growth and tumor cell metastasis. (2017)
  • Author(s): Yang X-Y
  • Organizer: 2017生命科学系学会合同年次大会 (ConBio2017)
  • Invited
• [Presentation] ヒト細胞のUV 照射による癌抑制分子CXCL14の発現上昇はp38デルタ特異的シグナル経路による (2017)
  • Author(s): 陽暁艶, 小澤重幸, 生駒丈晴, 鈴木健司, 岩渕博史, 前畑洋次郎, 宮本千央, 久保田英朗, 畑隆一郎
  • Organizer: 第49回日本結合組織学会学術大会
• [Presentation] p38delta MAP kinase specific pathway stimulates gene expression of chemokine CXCL14, a multistep tumor supprresor (2017)
  • Author(s): Yang X-Y, Ozawa Y, Ikoma T, Maehata Y, Kato Y, Hata R
  • Organizer: 第59回歯科基礎医学会学術大会
• [Presentation] Chemokine CXCL14 is a multifunctional guardian molecule: A promising molecular target for cancer therapy and prevention (2017)
  • Author(s): Yang X-Y, Ozawa S, Ikoma T, Suzuki K, Kanamori K, Kiyono T, Hata R
  • Organizer: 第76 回日本癌学会