Mammary tissue microenvironment determines T cell‐dependent breast cancer‐associated inflammation

Takahashi, Kei; Nagai, Naomi; Ogura, Keisuke; Tsuneyama, Koichi; Saiki, Ikuo; Irimura, Tatsuro; Hayakawa, Yoshihiro

doi:10.1111/cas.12685

Cited by 29 publications

(24 citation statements)

References 35 publications

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“…MCA205, a methylcholanthrene-induced murine fibrosarcoma cell line was kindly provided by Dr. S.A. Rosenberg (National Cancer Institute, Bethesda, MD) and maintained in complete RPMI 1640 medium. MCA205-Luc2 cells stably expressing luciferase with a CMV promoter were established as previously described (28). Briefly, MCA205 cells (5 Â 10 5 /well) were seeded in a 6-well plate and transfected with pGL4.50 vector using Lipofectamine 2000.…”

Section: Cells and Reagentsmentioning

confidence: 99%

NK Cells Control Tumor-Promoting Function of Neutrophils in Mice

Ogura

Sato-Matsushita

Yamamoto

et al. 2018

Cancer Immunology Research

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Although natural killer (NK) cells are recognized as direct antitumor effectors, the ability of NK cells to control cancer-associated inflammation, which facilitates tumor progression, remains unknown. In this study, we demonstrate that NK cells control tumor-promoting inflammation through functional modification of neutrophils. NK cells control the tumor-promoting function of neutrophils through an IFNγ-dependent mechanism. Tumor progression in an NK cell-depleted host is diminished when the IL17A-neutrophil axis is absent. In NK cell-depleted mice, neutrophils acquire a tumor-promoting phenotype, characterized by upregulation of VEGF-A expression, which promotes tumor growth and angiogenesis. A VEGFR inhibitor which preferentially suppressed tumor growth in NK cell-depleted mice was dependent on neutrophils. Furthermore, the systemic neutropenia caused by an antimetabolite treatment showed an anticancer effect only in mice lacking NK cells. Thus, NK cells likely control the tumor-promoting and angiogenic function of neutrophils.

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Section: Cells and Reagentsmentioning

confidence: 99%

NK Cells Control Tumor-Promoting Function of Neutrophils in Mice

Ogura

Sato-Matsushita

Yamamoto

et al. 2018

Cancer Immunology Research

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“…The selection of modeling methods varies in different studies, including tissue and cell inoculation, orthotopic implantation (OS), subcutaneous implantation (SQ) and tail vein injection (TV). As for the syngeneic model, the characteristic of tumor progression is related to the inocula, the implantation site and the number of inoculated cells ( 4 , 5 , 16 , 20 , 23 , 24 ). Therefore, a good understanding of the characteristics of models induced by distinct methods will aid investigators to make appropriate choices, according to the research requirements.…”

Section: Introductionmentioning

confidence: 99%

Establishment of a murine breast tumor model by subcutaneous or orthotopic implantation

Zhang

Sun

et al. 2018

Oncol Lett

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A number of murine models are used to mimic the pathology of breast cancer. Tissue inoculation and cell inoculation using orthotopic implantation (OS) and subcutaneous implantation (SQ) are commonly used to generate murine models to investigate cancer. However, limited information is available in regard to the variations of these methods. The present study compared growth, metastasis, survival and histopathology of tumors produced using OS and SQ to characterize features of the tumors produced by the two distinct methods. Additionally, the present study aimed at providing increased options for investigators when designing experiments. 4T1-luc2 cell suspension or 4T1-luc2 tissue suspension was inoculated using either OS or SQ into BALB/c mice. Tumor growth and metastasis were detected using an in vivo imaging system and calipers. Excised tumors and lung were assessed by tissue staining with hematoxylin and eosin, and the vessel marker cluster of differentiation 31. The results of the present study revealed that the cell suspension generated breast tumors of increased size, which was visualized and determined, following inoculation, using calipers at an earlier time point compared with tumors produced by tissue suspension. The increasing bioluminescent trend of OS tumors was more marked compared with that of SQ tumors. The volume of OS tumor was increased with decreased variation, compared with that of SQ tumors. In addition, the OS tumor exhibited increased microvessel density. Bioluminescent signals and histological results in regard to metastasis were consistent: OS implantation produced increased lung metastasis compared with that of SQ implantation, although they exhibited similar survival times. The results of the present study indicated that the inocula from distinct sources (tissue or cell) affected tumor growth. Furthermore, breast tumor progression and histopathological characteristics were distinct between OS and SQ, whereas OS exhibited increased malignant behavior. Understanding the characteristics of murine breast cancer models established by diverse methods may aid investigators to select appropriate animal models, according to the requirements of the study.

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“…All these clues led us to test the antitumor and antimetastatic effects of BDM in 4T1 breast cancer model, which is animal model for stage IV human breast cancer in immune competent BALB/c mice. Regarding the high metastatic capacity and inflammatory microenvironment of 4T1 tumor model, this model can better mimic the clinical situation compared to a mouse model bearing human tumor xenografts . In this study, we investigated the antiinflammatory and anticancer properties of BDM on 4T1 murine breast cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Targeting of crosstalk between tumor and tumor microenvironment by β‐D mannuronic acid (M2000) in murine breast cancer model

et al. 2017

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Metastasis is the main cause of death in breast cancer patients. Inflammatory processes following crosstalk between tumor cells and tumor microenvironment play an important role in progression and metastasis of cancer. Hence, targeting of these interactions may represent a novel promising strategy for breast cancer therapy. So, we investigated the effects of β‐D mannuronic acid (BDM), a new antiinflammatory agent, on 4T1 breast cancer cell line both in vitro and in vivo. Proliferation assays revealed low‐cytotoxic effect of BDM on 4T1 cells. However, BDM reduced activity of MMP‐2, MMP‐9 and significantly decreased the adhesion of 4T1 cells to extracellular matrix (ECM) in a dose‐dependent manner. The in vivo results demonstrated that BDM strongly inhibits tumor growth and increases lifespan as compared with control mice. The decrease in tumor mass was associated with decreased metastasis, recruitment, and frequency of inflammatory cells in tumor tissue. Our preclinical findings demonstrated that BDM therapy not only prevents formation of chronic inflammatory response but also inhibits crosstalk between tumor cells and their microenvironment, which is associated with reduction of tumor growth and metastasis arrest. Our data imply the use of BDM therapy in future clinical trials to open a new horizon for breast cancer therapy.

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Mammary tissue microenvironment determines T cell‐dependent breast cancer‐associated inflammation

Cited by 29 publications

References 35 publications

NK Cells Control Tumor-Promoting Function of Neutrophils in Mice

NK Cells Control Tumor-Promoting Function of Neutrophils in Mice

Establishment of a murine breast tumor model by subcutaneous or orthotopic implantation

Targeting of crosstalk between tumor and tumor microenvironment by β‐D mannuronic acid (M2000) in murine breast cancer model

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