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

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. (April 2012) Imaging Tumor-Stroma Interactions during Chemotherapy Reveals Contributions of the Microenvironment to Resistance. Cancer Cell, 21 (4). pp. 488-503. ISSN 1535-6108

URL: http://www.ncbi.nlm.nih.gov/pubmed/22516258
DOI: 10.1016/j.ccr.2012.02.017

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.

Item Type: Paper
Uncontrolled Keywords: breast-cancer model drug-resistance in-vivo cell-death tgf-beta recruitment mice macrophages inhibition delivery
Subjects: diseases & disorders > cancer
diseases & disorders
diseases & disorders > cancer > drugs and therapies > chemotherapy
diseases & disorders > cancer > drugs and therapies
CSHL Authors:
Communities: CSHL Cancer Center Program > Signal Transduction
CSHL Cancer Center Shared Resources > Animal Services
CSHL Cancer Center Shared Resources > Flow Cytometry Service
CSHL Cancer Center Shared Resources > Microscopy Service
CSHL Post Doctoral Fellows
CSHL labs > Egeblad lab
Watson School > Publications
CSHL Cancer Center Shared Resources > Animal Tissue and Imaging Service
Depositing User: Matt Covey
Date: April 2012
Date Deposited: 30 Jan 2013 16:46
Last Modified: 29 Oct 2015 20:19
PMCID: PMC3332002
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27010

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