Cancer Cell
Volume 21, Issue 4, 17 April 2012, Pages 488-503
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Article
Imaging Tumor-Stroma Interactions during Chemotherapy Reveals Contributions of the Microenvironment to Resistance

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Summary

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.

Highlights

► Mechanisms extrinsic to cancer cells regulate chemoresistance in breast cancer ► Imaging shows the best drug penetration and response at intermediate tumor stages ► Myeloid cells are recruited to doxorubicin-treated tumors via the CCR2 receptor ► Vascular permeability and myeloid cells influence the response to chemotherapy

Cited by (0)

10

These authors contributed equally to this work

11

These authors contributed equally to this work