Comparison of the Adipose and Luminal Mammary Gland Compartment as Orthotopic Inoculation Sites in a 4T1-Based Immunocompetent Preclinical Model for Triple-Negative Breast Cancer

2016 ◽  
Vol 21 (3-4) ◽  
pp. 113-122 ◽  
Author(s):  
Jonas Steenbrugge ◽  
Koen Breyne ◽  
Sofie Denies ◽  
Melissa Dekimpe ◽  
Kristel Demeyere ◽  
...  
2020 ◽  
Vol 9 (1) ◽  
pp. 1830524
Author(s):  
Karsten A. Pilones ◽  
Michal Hensler ◽  
Camille Daviaud ◽  
Jeffrey Kraynak ◽  
Jitka Fucikova ◽  
...  

2017 ◽  
Vol 30 (11) ◽  
pp. e3799 ◽  
Author(s):  
Stephanie L. Barnes ◽  
Anna G. Sorace ◽  
Jennifer G. Whisenant ◽  
J. Oliver McIntyre ◽  
Hakmook Kang ◽  
...  

2019 ◽  
Author(s):  
Justyna Zdrojewska ◽  
Mari I. Suominen ◽  
Katja M. Fagerlund ◽  
Jussi M. Halleen ◽  
Jenni Bernoulli ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2686
Author(s):  
Zongsheng He ◽  
Abdel-Majid Khatib ◽  
John W. M. Creemers

In triple negative breast cancer (TNBC) cell lines, the proprotein convertase Furin cleaves and then activates several protein precursors involved in oncogenesis. However, the in vivo role of Furin in the mammary gland and how mammary gland-specific Furin knockout specifically influences tumor initiation and progression of TNBC is unknown. Here, we report that Furin is frequently overexpressed in TNBC tumors and this correlates with poor prognosis in patients with TNBC tumors. In a whey acidic protein (WAP)-induced mammary epithelial cell-specific Furin knockout mouse model, mice show normal mammary development. However, loss of Furin in mammary glands inhibits primary tumor growth and lung metastasis in an oncogene-induced TNBC mouse model. Further analysis of TNBC mice lacking Furin revealed repressed maturation of the Furin substrates proIGF1R and proIR that are associated with reduced expression and activation of their downstream effectors PI3K/AKT and MAPK/ERK1/2. In addition, these tissues showed enhanced apoptotic signaling. In conclusion, our findings reveal that upregulated Furin expression reflects the poor prognosis of TNBC patients and highlights the therapeutic potential of inhibiting Furin in TNBC tumors.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Toshihiro Yokoi ◽  
Takaaki Oba ◽  
Ryutaro Kajihara ◽  
Scott I. Abrams ◽  
Fumito Ito

AbstractDespite recent progress in therapeutic strategies, prognosis of metastatic triple-negative breast cancer (TNBC) remains dismal. Evidence suggests that the induction and activation of tumor-residing conventional type-1 dendritic cells (cDC1s) is critical for the generation of CD8+ T cells that mediate the regression of mammary tumors and potentiate anti-PD-1/PD-L1 therapeutic efficacy. However, it remains unknown whether this strategy is effective against metastatic TNBC, which is poorly responsive to immunotherapy. Here, using a mouse model of TNBC, we established orthotopic mammary tumors and brain metastases, and treated mammary tumors with in situ immunomodulation (ISIM) consisting of intratumoral injections of Flt3L to mobilize cDC1s, local irradiation to induce immunogenic tumor cell death, and TLR3/CD40 stimulation to activate cDC1s. ISIM treatment of the mammary tumor increased circulating T cells with effector phenotypes, and infiltration of CD8+ T cells into the metastatic brain lesions, resulting in delayed progression of brain metastases and improved survival. Furthermore, although anti-PD-L1 therapy alone was ineffective against brain metastases, ISIM overcame resistance to anti-PD-L1 therapy, which rendered these tumor-bearing mice responsive to anti-PD-L1 therapy and further improved survival. Collectively, these results illustrate the therapeutic potential of multimodal intralesional therapy for patients with unresectable and metastatic TNBC.


PLoS ONE ◽  
2018 ◽  
Vol 13 (4) ◽  
pp. e0192689 ◽  
Author(s):  
Arvind Bambhroliya ◽  
Renae D. Van Wyhe ◽  
Swaminathan Kumar ◽  
Bisrat G. Debeb ◽  
Jay P. Reddy ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document