The treatment strategy for highly therapy resistant subfractions of cancer stem cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K14589
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Osaka University
• Principal Investigator: Shimpei Nishikawa 大阪大学, 医学系研究科, 招へい教員 (90730565)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 癌幹細胞 / 犬 / 伴侶動物 / 乳腺腫瘍 / 乳癌 / 比較腫瘍学 / 抗癌剤 / 表面抗原

Outline of Final Research Achievements

Mammary gland tumor (MGT) is one of the most common neoplastic disease in both dogs and humans. However, therapeutic options are limited for advanced unresectable metastatic MGTs. Cancer stem cells (CSCs) have been reported to be one of the mechanism of therapeutic resistance of dog MGTs (dMGTs). However, detailed mechanism(s) of therapeutic resistance of CSCs in dMGTs is not fully understood. To elucidate the therapeutic resistance mechanism(s) of dMGTs, the screening of surface markers expression using cell lines of dMGTs was performed. The expressions of several candidate markers were detected in dMGT cell lines under adherent and sphere culture conditions, and under the presense of chemotherapeutic agent doxorubicin by using flowcytometry. Several markers showed significantly higher expression after exposure to doxorubicin. The markers identified in the screening are now further analyzed for function in therapeutic resistant CSCs of dMGTs.

Free Research Field

腫瘍学

Academic Significance and Societal Importance of the Research Achievements

浸潤・転移により切除不能な犬乳腺腫瘍に対して有効性の高い治療法はないのが現状である。近年、癌組織中に「癌幹細胞」が存在し、治療抵抗性等に関与することが、人間におけるほとんど全ての悪性腫瘍において知られている。犬乳腺腫瘍においても癌幹細胞の存在を示唆する報告が相次いでいる。本研究では、犬乳腺腫瘍幹細胞の治療ターゲットとなり得るマーカーを複数同定することができた。今後の創薬応用への展開が期待できる。