Identification and characterization of endothelium-derived factors that promote melanoma stem cells

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860883
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Ehime University
• Principal Investigator: Shiraiahi Ken 愛媛大学, 医学部附属病院, 講師 (80710863)
• Co-Investigator(Renkei-kenkyūsha): Murakami Masamoto 愛媛大学, 医学部付属病院, 講師 (20278302) ; Hanakawa Yasushi 愛媛大学, 医学部付属病院, 講師 (90284398)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: メラノーマ / 癌幹細胞 / リンパ管内皮 / ニッチ

Outline of Final Research Achievements

Co-culture of lymphatic endothelial cells (LECs) with melanoma stem cells revealed that LECs promoted the self-renewal of melanoma stem cells, as evidenced by increased sphere formation capacity. Using RT-PCR-based transcriptional profiling, we found that the chemokines CXCL9, CXCL10 and CXCL11 were strongly expressed by LECs when co-cultured with CSCs. Addition of recombinant CXCL10 or CXCL11 promoted sphere formation of melanoma stem cells, and sphere formation was significantly inhibited by a CXCR3 neutralizing antibody. The expression of CXCR3 was strongly increased in sphere-forming melanoma cells compared to melanoma cells in adherent cultures and that CXCR3 is also expressed by a subpopulation of tumor cells in human malignant melanomas of the skin. Together, these findings indicate an important role of CXCR3 activation in the maintenance of CSCs and suggest that CXCR3 blockade might represent a novel therapeutic strategy to specifically target melanoma stem cells.

Free Research Field

皮膚悪性腫瘍