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

被引：397

作者：

Nakasone, Elizabeth S. ^{[1
,2
]}

Askautrud, Hanne A. ^{[1
,3
,4
,5
]}

Kees, Tim ^{[1
]}

Park, Jae-Hyun ^{[1
]}

Plaks, Vicki ^{[3
]}

Ewald, Andrew J. ^{[3
,6
,7
]}

Fein, Miriam ^{[1
,8
]}

Rasch, Morten G. ^{[1
,9
]}

Tan, Ying-Xim ^{[3
]}

Qiu, Jing ^{[1
]}

Park, Juwon ^{[1
]}

Sinha, Pranay ^{[1
]}

Bissell, Mina J. ^{[10
]}

Frengen, Eirik ^{[4
,5
]}

Werb, Zena ^{[3
]}

Egeblad, Mikala ^{[1
,3
]}

机构：

[1] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA

[2] Watson Sch Biol Sci, Cold Spring Harbor, NY 11724 USA

[3] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA

[4] Univ Oslo, Inst Clin Med, Dept Med Genet, N-0315 Oslo, Norway

[5] Oslo Univ Hosp, Dept Med Genet, N-0424 Oslo, Norway

[6] Johns Hopkins Sch Med, Ctr Cell Dynam, Dept Cell Biol, Baltimore, MD 21205 USA

[7] Johns Hopkins Sch Med, Ctr Cell Dynam, Dept Oncol, Baltimore, MD 21205 USA

[8] SUNY Stony Brook, Grad Program Genet, Stony Brook, NY 11794 USA

[9] Copenhagen Univ Hosp, Finsen Lab, DK-1165 Copenhagen, Denmark

[10] Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA

来源：

CANCER CELL | 2012年 / 21卷 / 04期

关键词：

BREAST-CANCER MODEL; DRUG-RESISTANCE; IN-VIVO; CELL-DEATH; TGF-BETA; RECRUITMENT; MICE; MACROPHAGES; INHIBITION; DELIVERY;

D O I：

10.1016/j.ccr.2012.02.017

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：488 / 503

页数：16

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