Role of tumor-associated macrophages on response to chemotherapy in colon cancer

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591971
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Suzuka University of Medical Science
• Principal Investigator: YONEDA Misao 鈴鹿医療科学大学, 保健衛生学部, 准教授 (60600492)
• Co-Investigator(Kenkyū-buntansha): SHIRAISHI Taizo 三重大学, 大学院医学系研究科, 教授 (30162762) ; HIROKAWA Yoshifumi 三重大学, 大学院医学系研究科, 講師 (30322738) ; ISHII Kenichiro 三重大学, 大学院医学系研究科, 助教 (90397513)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 大腸癌 / 化学療法薬耐性獲得 / 腫瘍関連マクロファージ / 癌幹細胞ニッチ / IL1B / ナフトピジル / スフェロイド形成

Outline of Final Research Achievements

In the tumor microenvironment, tumor-associated macrophages (TAMs) are considered to play a critical role in the regulation of cancer stem/initiating cells. In this study, we hypothesized that TAMs may be involved in the response to chemotherapy. To explore the effective drug for inhibiting induction of TAMs-like differentiation in normal macrophages s by cancer cells, we performed in vitro co-culture experiments. In in vitro co-culture of PMA-THP-1 cells with human colon cancer cell lines, IL1B mRNA was upregulated by co-culturing with HT29 cells. Among 4 phenylpiperazine derivatives, only naftopidil showed anti-proliferative activity on human colon cancer cell lines. Induction of TAMs-like differentiation in PMA-THP-1 cells by co-culturing with HT29 cells was completely cancelled by naftopidil. Our data suggested strongly that naftopidil might be effective in inhibiting induction of TAMs-like differentiation in normal macrophages by colon cancer cells.

Free Research Field

医歯薬学