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
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 School of Biological Sciences > 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: | https://repository.cshl.edu/id/eprint/27010 |
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