scholarly journals Activation of the Aryl Hydrocarbon Receptor by TCDD Inhibits Mammary Tumor Metastasis in a Syngeneic Mouse Model of Breast Cancer

2011 ◽  
Vol 124 (2) ◽  
pp. 291-298 ◽  
Author(s):  
Tao Wang ◽  
Katie L. Wyrick ◽  
Gary G. Meadows ◽  
Tamara B. Wills ◽  
Beth A. Vorderstrasse
2021 ◽  
Vol 12 ◽  
Author(s):  
Christoph F. A. Vogel ◽  
Gwendal Lazennec ◽  
Sarah Y. Kado ◽  
Carla Dahlem ◽  
Yi He ◽  
...  

Activation of the aryl hydrocarbon receptor (AhR) through environmental exposure to known human carcinogens including dioxins can lead to the promotion of breast cancer. While the repressor protein of the AhR (AhRR) blocks the canonical AhR pathway, the function of AhRR in the development of breast cancer is not well-known. In the current study we examined the impact of suppressing AhR activity using its dedicated repressor protein AhRR. AhRR is a putative tumor suppressor and is silenced in several cancer types, including breast, where its loss correlates with shorter patient survival. Using the AhRR transgenic mouse, we demonstrate that AhRR overexpression opposes AhR-driven and inflammation-induced growth of mammary tumors in two different murine models of breast cancer. These include a syngeneic model using E0771 mammary tumor cells as well as the Polyoma Middle T antigen (PyMT) transgenic model. Further AhRR overexpression or knockout of AhR in human breast cancer cells enhanced apoptosis induced by chemotherapeutics and inhibited the growth of mouse mammary tumor cells. This study provides the first in vivo evidence that AhRR suppresses mammary tumor development and suggests that strategies which lead to its functional restoration and expression may have therapeutic benefit.


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi199-vi199
Author(s):  
Ramin Morshed ◽  
Alexander Haddad ◽  
Saket Jain ◽  
Sabraj Gill ◽  
Jordan Spatz ◽  
...  

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.


2017 ◽  
Vol 8 ◽  
Author(s):  
Jenna N. Regan ◽  
Carter Mikesell ◽  
Steven Reiken ◽  
Haifang Xu ◽  
Andrew R. Marks ◽  
...  

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Katie M. Parkins ◽  
Veronica P. Dubois ◽  
Amanda M. Hamilton ◽  
Ashley V. Makela ◽  
John A. Ronald ◽  
...  

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2320
Author(s):  
Hemavathy Subramaiam ◽  
Wan-Loy Chu ◽  
Ammu Kutty Radhakrishnan ◽  
Srikumar Chakravarthi ◽  
Kanga Rani Selvaduray ◽  
...  

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.


2013 ◽  
Vol 24 ◽  
pp. iii40 ◽  
Author(s):  
S. Irshad ◽  
F. Flore Flores-Borja ◽  
R. Evans ◽  
G. Fruhwirth ◽  
J. Monypenny Pitmilly ◽  
...  

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