Imaging tumor-stroma interactions during chemotherapy reveals contributions of the microenvironment to resistance (Cancer Cell, 2012, 21:488-503)

報告日期: 2012/10/12
報告時間: 16:00/16:50
報告學生: 紀智瑛
講評老師: 陳玉玲
附件下載: 下載[1230-1348725154-1.pdf] 

Imaging Tumor-Stroma Interactions during Chemotherapy Reveals Contributions of the Microenvironment to Resistance

Elizabeth S. Nakasone, Hanne A. Askautrud, Tim Kees, Jae-Hyun Park, Vicki Plaks, Andrew J. Ewald, Miriam Fein, Morten G. Rasch, Ying-Xim Tan, Jing Qiu, Juwon Park, Pranay Sinha, Mina J. Bissell, Eirik Frengen, Zena Werb, Mikala Egeblad

Cancer Cell. 2012 Apr 17;21(4):488-503

PresenterJhih-Ying Chi               Date/Time2012/10/12 1710-1800

CommentatorYuh-Ling Chen, Ph.D.     Place602, College of medicine

Abstract

In vivo imaging of therapy responses in a progressive breast cancer model and revealed that chemosensitivity is influenced by the tumor microenvironment. Using intravital microscopy of tumors allowed us to know drug distribution, cell death, vascular leakage and myeloid cell infiltration. The highest sensitivity to doxorubicin was observed in the early carcinoma stage. These differences in drug response between stages were associated with differences in vascular leakage. Then, the authors tested doxorubicin response in matrix metalloproteinase-9 null mice that showed increased vascular leakage and had an improved response. In addition, a vascular leakage was associated with higher infiltration of myeloid cell. The authors therefore determined the effect of MMP9 on myeloid cell infiltration. The result showed that doxorubicin led to recruitment of myeloid cells to tumor in MMP9 null microenvironment or more vascular leakage condition. Furthermore, the authors identify the attractable chemokines and cell types of myeloid cells. They found that monocytic cells were recruited to doxorubicin-treated tumors via the CCR2 receptor. In Ccr2 null microenvironments, recruitment was inhibited and the response to chemotherapy better. These data suggest that vascular permeability and myeloid cells influence the response to chemotherapy.

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