Osteolytic Breast Cancer Causes Skeletal Muscle Weakness in an Immunocompetent Syngeneic Mouse Model

Abstract Breast cancer is the most common malignancy in women in the United States, and brain metastases occur in almost a third of patients with metastatic dissemination. Immunoediting is a critical component of metastatic tumor cell elimination, and tumor clones that develop immune-escape mechanisms are associated with progression and metastatic dissemination. We hypothesized that breast cancer brain metastatic cells harbor immunomodulatory cytokine expression changes that promote an immunosuppressive environment to avoid immune cell-mediated elimination. To study this, a syngeneic mouse model of metastatic breast cancer was used. A brain metastatic line derived from the 4T1 breast cancer parental cell line was created by serially selecting brain metastatic populations of cells after intracardiac injection (4T1 BrM). A gene-expression analysis using an 800-gene cancer immunology-specific microarray panel was performed comparing the 4T1 parental and 4T1 BrM lines. 4T1 BrM cells demonstrate gene expression changes promoting immunosuppression including significant upregulation of IL18 and Lgals9 (Galectin-9) and downregulation of CD40, IL2rg, CCL2, and EOMES. When compared to 4T1 parental lines, the 4T1 BrM line demonstrated decreased expression of CCL2 and increased expression of GM-CSF on a cytokine array, corresponding to results obtained from gene expression analysis. These results suggest tumor-intrinsic cytokine expression changes that may mediate an immunosuppressive environment.

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A motor axonopathy in a mouse model of Duchenne Muscular Dystrophy

10.1101/2020.01.22.914614 ◽

2020 ◽

Author(s):

Justin S. Dhindsa ◽

Angela L. McCall ◽

Laura M. Strickland ◽

Anna F. Fusco ◽

Amanda F. Kahn ◽

...

Keyword(s):

Skeletal Muscle ◽

Respiratory Failure ◽

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Mouse Model ◽

Cause Of Death ◽

Muscle Weakness ◽

Common Cause ◽

Skeletal Muscle Weakness ◽

Nerve Dysfunction

AbstractSkeletal muscle weakness due to loss of dystrophin is a well-documented pathological hallmark of Duchenne muscular dystrophy (DMD). In contrast, the neuropathology of this disease remains understudied. Here, we characterize an axonopathy in the phrenic and hypoglossal (XII) nerves of mdx mice. We observe nerve dysfunction that we propose contributes to respiratory failure, the most common cause of death in DMD.

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Multimodality cellular and molecular imaging of concomitant tumour enhancement in a syngeneic mouse model of breast cancer metastasis

Scientific Reports ◽

10.1038/s41598-018-27208-4 ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 1

Author(s):

Katie M. Parkins ◽

Veronica P. Dubois ◽

Amanda M. Hamilton ◽

Ashley V. Makela ◽

John A. Ronald ◽

...

Keyword(s):

Breast Cancer ◽

Molecular Imaging ◽

Mouse Model ◽

Cancer Metastasis ◽

Breast Cancer Metastasis ◽

Syngeneic Mouse ◽

Syngeneic Mouse Model

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Evaluating Anticancer and Immunomodulatory Effects of Spirulina (Arthrospira) platensis and Gamma-Tocotrienol Supplementation in a Syngeneic Mouse Model of Breast Cancer

Nutrients ◽

10.3390/nu13072320 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2320

Author(s):

Hemavathy Subramaiam ◽

Wan-Loy Chu ◽

Ammu Kutty Radhakrishnan ◽

Srikumar Chakravarthi ◽

Kanga Rani Selvaduray ◽

...

Keyword(s):

Breast Cancer ◽

Mouse Model ◽

T Regulatory Cells ◽

Arthrospira Platensis ◽

Host Immune Responses ◽

Syngeneic Mouse ◽

Anticancer Effects ◽

Syngeneic Mouse Model ◽

4T1 Cells ◽

Gamma Tocotrienol

Nutrition can modulate host immune responses as well as promote anticancer effects. In this study, two nutritional supplements, namely gamma-tocotrienol (γT3) and Spirulina, were evaluated for their immune-enhancing and anticancer effects in a syngeneic mouse model of breast cancer (BC). Five-week-old female BALB/c mice were fed Spirulina, γT3, or a combination of Spirulina and γT3 (Spirulina + γT3) for 56 days. The mice were inoculated with 4T1 cells into their mammary fat pad on day 28 to induce BC. The animals were culled on day 56 for various analyses. A significant reduction (p < 0.05) in tumor volume was only observed on day 37 and 49 in animals fed with the combination of γT3 + Spirulina. There was a marked increase (p < 0.05) of CD4/CD127+ T-cells and decrease (p < 0.05) of T-regulatory cells in peripheral blood from mice fed with either γT3 or Spirulina. The breast tissue of the combined group showed abundant areas of necrosis, but did not prevent metastasis to the liver. Although there was a significant increase (p < 0.05) of MIG-6 and Cadherin 13 expression in tumors from γT3-fed animals, there were no significant (p > 0.05) differences in the expression of MIG-6, Cadherin 13, BIRC5, and Serpine1 upon combined feeding. This showed that combined γT3 + Spirulina treatment did not show any synergistic anticancer effects in this study model.

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