19:10 - 21:00
Room: Ishikawa Ongakudō Interchange Hall
Poster Session
Rb inactivation enhances tumor progression by elevating CCL2 expression.
Fengkai Li1, Shunsuke Kitajima1, 2, Naofumi Mukaida3, Chiaki Takahashi1
1Division of Oncology and Molecular Biology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan, 2Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, United States, 3Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Japan

[Introduction] Breast cancer is the leading cause of cancer mortality in 40s-60s Japanese women. The p53 mutation is common in breast cancer. In preclinical models, additional inactivation of Rb is often associated with gain of undifferentiated phenotype or therapy resistance.

[Methods] We determined Rb inactivation signature in a p53-null genetic background. We previously reported that the p53-null genetic background facilitated us to investigate novel Rb functions in controlling undifferentiated state. We thought the presence of p53 might counterbalance the effect of Rb inactivation on various cellular functions. We therefore first employed a sarcoma cell line established from a p53-/- mouse to determine the Rb inactivation signature by RNA-seq. We then employed a breast cancer cell line MCF-7 to obtain a relevance of the findings in p53-null soft tissue sarcoma cells. MCF-7 is lacking expression of ARF; most probably because of this, Rb inactivation does not induce p53 activation in MCF-7 cells.

[Results] We identified CCL2 as one of the most significantly altered gene in the Rb inactivation signature. We found that Rb inactivation increases the CCL2 expression level in a mouse p53-null sarcoma cell line and in MCF7. Rb inactivation in sarcoma cells significantly enhanced recruitment of CD11b+;Gr-1+ MDSC when transplanted into C57BL/6 mice. Additionally, CCR2-null background antagonized this effect of Rb inactivation. In a trans-well assay, CCL2 neutralization using an antibody antagonized chemo-attraction of THP-1 cells induced by Rb inactivation in MCF-7 cells. These findings suggest that Rb inactivation increases CCL2 expression hence facilitates aggressiveness in sarcoma and breast cancer cells.

[Conclusion] This study proposes that the CCL2 might be a promising therapeutic target in breast cancer.


Reference:
Tu-P14-40
Session:
Poster Session 14 “Cytokines in cancer development and antitumor immune therapy”
Presenter/s:
Fengkai Li
Presentation type:
Poster Presentation
Room:
Ishikawa Ongakudō Interchange Hall
Date:
Tuesday, 31 October 2017
Time:
19:10 - 21:00
Session times:
19:10 - 21:00