A search for novel cancer stem cell marker of cutaneous squamous cell carcinoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K08273
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: University of the Ryukyus
• Principal Investigator: TAKEI KIMIKO 琉球大学, 病院, 助教 (90325861)
• Co-Investigator(Kenkyū-buntansha): 海川 正人 琉球大学, 医学(系)研究科(研究院), 准教授 (00325838) ; 丸山 一郎 沖縄科学技術大学院大学, 情報処理生物学ユニット, 教授 (70426568)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 有棘細胞癌 / TAM / Rap2

Outline of Final Research Achievements

Pam212, a mouse keratinocyte cell line expresses Rap2, are non-metastatic. In contrast, metastatic derivatives of Pam212 cells expressed extremely low levels of Rap2. We have found that Rap2 is expressed in tumor invasive monocytes (CD68 positive) in SCC tissue specimens. Rap2 is Ras-like small G protein, and has three isotypes, Rap2A, Rap2B and Rap2C. Rap2B expression in murine bone marrow-derived cells was up-regulated by macrophage colony stimulation factor (MCSF). No difference in growth and morphology was found when bone marrow-derived cells from wild-type and Rap2B KO mice were stimulated by MCSF. There are two types of macrophages, inflammatory phenotype (M1) and regenerative phenotype (M2). Tumor associated macrophage (TAM) promote cancer metastasis like M2 by enhancing angiogenesis as well as tumor cell growth, migration and invasion. Rap2 function in TAM is under investigation using Rap2B KO mice.

Free Research Field

皮膚腫瘍

Academic Significance and Societal Importance of the Research Achievements

Rap2は癌遺伝子産物であるRasの類縁体でありながら、悪性腫瘍における機能の詳細は未だ不明である。今回、ヒト有棘細胞癌の腫瘍浸潤マクロファージにおけるRap2の関与を新規に見出した。Rap2の機能を制御することで根治切除困難な有棘細胞癌症例に対する新しい治療方法が開発出来る可能性がある。