@article{abe5a218d3f647b4aca071a4db070ccb,
title = "Imaging Tumor-Stroma Interactions during Chemotherapy Reveals Contributions of the Microenvironment to Resistance",
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.",
author = "Nakasone, {Elizabeth S.} and Askautrud, {Hanne A.} and Tim Kees and Park, {Jae Hyun} and Vicki Plaks and Ewald, {Andrew J.} and Miriam Fein and Rasch, {Morten G.} and Tan, {Ying Xim} and Jing Qiu and Juwon Park and Pranay Sinha and Bissell, {Mina J.} and Eirik Frengen and Zena Werb and Mikala Egeblad",
note = "Funding Information: We thank E. Atamaniuc, Y. Yu, H. Capili, J. Cappellani, G. DiMino, M.B. Ebert, J. Waage, J. Paterek, and the Shared Resources at CSHL for technical support. Dr. Claire Lewis is thanked for helpful comments on the manuscript. Antibodies against BrdU and MECA-32 were obtained from the Developmental Studies Hybridoma Bank maintained by the University of Iowa. This work was supported by funds from the National Cancer Institute (U01 CA141451 to M.E.; R01 CA057621 to Z.W. and M.J.B.; and P50 CA088843 to A.J.E.), the Starr Cancer Consortium, the Breast Cancer Alliance, Susan G. Komen for the Cure, Long Island 2 Day Walk to Fight Breast Cancer and Manhasset Women's Coalition Against Breast Cancer to M.E., the Stand Up to Cancer-American Association for Cancer Research Dream Team Translational Cancer Research Grant (SU2C-AACR-DT0409 to Z.W.), a predoctoral fellowship from the Congressionally Directed Breast Cancer Research Program, U.S. (E.S.N.), the Research Council of Norway (160698/V40 and 151882 [FUGE] to E.F.), and Southeastern Regional Health Authorities (2007060 to E.F.). E.S.N. is the recipient of the Leslie C. Quick and William Randolph Hearst Foundation Fellowships from the Watson School of Biological Sciences. E.F. and H.A.A. were supported by “University of Oslo Research Fund (UNIFOR)” and Ullev{\aa}l University Hospital Research Fund (VIRUUS). ",
year = "2012",
month = apr,
day = "17",
doi = "10.1016/j.ccr.2012.02.017",
language = "English (US)",
volume = "21",
pages = "488--503",
journal = "Cancer cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "4",
}