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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)488-503
Number of pages16
JournalCancer cell
Volume21
Issue number4
DOIs
StatePublished - Apr 17 2012

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ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Nakasone, E. S., Askautrud, H. A., Kees, T., Park, J. H., Plaks, V., Ewald, A. J., Fein, M., Rasch, M. G., Tan, Y. X., Qiu, J., Park, J., Sinha, P., Bissell, M. J., Frengen, E., Werb, Z., & Egeblad, M. (2012). Imaging Tumor-Stroma Interactions during Chemotherapy Reveals Contributions of the Microenvironment to Resistance. Cancer cell, 21(4), 488-503. https://doi.org/10.1016/j.ccr.2012.02.017