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

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• 作者：Elizabeth  ; S. Nakasone¹ ; ² ; ¹⁰ ; Hanne  ; A. Askautrud¹ ; ³ ; ⁴ ; ⁵ ; ¹⁰ ; Tim Kees¹ ; Jae-Hyun Park¹ ; Vicki Plaks³ ; Andrew  ; J. Ewald³ ; ⁶ ; Miriam Fein¹ ; ⁷ ; Morten  ; G. Rasch¹ ; ⁸ ; Ying-Xim Tan³ ; Jing Qiu¹ ; Juwon Park¹ ; Pranay Sinha¹ ; Mina  ; J. Bissell⁹ ; Eirik Frengen⁴ ; ⁵ ; Zena Werb³ ; ¹¹ ; Mikala Egeblad¹ ; ³ ; ¹¹ ; ^{egeblad@cshl.edu}
• 刊名：Cancer Cell
• 出版年：2012
• 出版时间：17 April, 2012
• 年：2012
• 卷：21
• 期：4
• 页码：488-503
• 全文大小：3943 K

文摘

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Summary

Little is known about the dynamics of cancer cell death in response to therapy in the tumor microenvironment. Intravital microscopy of chemotherapy-treated mouse mammary carcinomas allowed us to follow drug distribution, cell death, and tumor-stroma interactions. We observed associations between vascular leakage and response to doxorubicin, including improved response in matrix metalloproteinase-9 null mice that had increased vascular leakage. Furthermore, we observed CCR2-dependent infiltration of myeloid cells after treatment and that Ccr2 null host mice responded better to treatment with doxorubicin or cisplatin. These data show that the microenvironment contributes critically to drug response via regulation of vascular permeability and innate immune cell infiltration. Thus, live imaging can be used to gain insights into drug responses in?situ.