期刊
CANCER SCIENCE
卷 106, 期 7, 页码 867-874出版社
WILEY
DOI: 10.1111/cas.12685
关键词
Breast cancer; imaging; inflammation; T cell; tissue microenvironment
类别
资金
- Tokyo Biochemical Research Foundation
- Cancer Research Institute, Kanazawa University
- Japan Society for the Promotion of Science
- Grants-in-Aid for Scientific Research [25293011, 15J11569, 15K08902] Funding Source: KAKEN
Although the importance of the host tissue microenvironment in cancer progression and metastasis has been established, the spatiotemporal process establishing a cancer metastasis-prone tissue microenvironment remains unknown. In this study, we aim to understand the immunological character of a metastasis-prone microenvironment in a murine 4T1 breast tumor model, by using the activation of nuclear factor-b (NF-B) in cancer cells as a sensor of inflammatory status and by monitoring its activity by bioluminescence imaging. By using a 4T1 breast cancer cell line stably expressing an NF-B/Luc2 reporter gene (4T1 NF-B cells), we observed significantly increased bioluminescence approximately 7days after metastasis-prone orthotopic mammary fat-pad inoculation but not ectopic s.c. inoculation of 4T1 NF-B cells. Such invivo NF-B activation within the fat-pad 4T1 tumor was diminished in immune-deficient SCID or nude mice, or T cell-depleted mice, suggesting the requirement of host T cell-mediated immune responses. Given the fat-pad 4T1 tumor expressed higher inflammatory mediators in a T cell-dependent mechanism compared to the s.c. tumor, our results imply the importance of the surrounding tissue microenvironment for inflaming tumors by collaborating with T cells to instigate metastatic spread of 4T1 breast cancer cells.
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