Progression to Malignancy in the Polyoma Middle T Oncoprotein Mouse Breast Cancer Model Provides a Reliable Model for Human Diseases
Elaine Y. Lin,Joan G. Jones,Ping Li,Liyin Zhu,Kathleen Whitney,William J. Muller,Jeffrey W. Pollard +6 more
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TLDR
The PyMT mouse model is demonstrated to be an excellent one to understand the biology of tumor progression in humans, and its comparison to human breast tumors is compared.Abstract:
Animal models are powerful tools to analyze the mechanism of the induction of human breast cancer. Here we report a detailed analysis of mammary tumor progression in one mouse model of breast cancer caused by expression of the polyoma middle T oncoprotein (PyMT) in the mammary epithelium, and its comparison to human breast tumors. In PyMT mice, four distinctly identifiable stages of tumor progression from premalignant to malignant stages occur in a single primary tumor focus and this malignant transition is followed by a high frequency of distant metastasis. These stages are comparable to human breast diseases classified as benign or in situ proliferative lesions to invasive carcinomas. In addition to the morphological similarities with human breast cancer, the expression of biomarkers in PyMT-induced tumors is also consistent with those associated with poor outcome in humans. These include a loss of estrogen and progesterone receptors as well as integrin-beta1 expression and the persistent expression of ErbB2/Neu and cyclinD1 in PyMT-induced tumors as they progress to the malignant stage. An increased leukocytic infiltration was also closely associated with the malignant transition. This study demonstrates that the PyMT mouse model is an excellent one to understand the biology of tumor progression in humans.read more
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Collagen reorganization at the tumor-stromal interface facilitates local invasion
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TL;DR: Three tumor-associated collagen signatures (TACS) are observed and defined that provide novel markers to locate and characterize tumors and should provide indications that a tumor is, or could become, invasive, and may serve as part of a strategy to help identify and characterize breast tumors in animal and human tissues.
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Leukocyte Complexity Predicts Breast Cancer Survival and Functionally Regulates Response to Chemotherapy
David G. DeNardo,David G. DeNardo,Donal J. Brennan,Elton Rexhepaj,Brian Ruffell,Stephen L. Shiao,Stephen F. Madden,William M. Gallagher,Nikhil Wadhwani,Scott D. Keil,Sharfaa A. Junaid,Hope S. Rugo,E. Shelley Hwang,Karin Jirström,Brian L. West,Lisa M. Coussens +15 more
TL;DR: Blockade of pathways mediating macrophage recruitment, in combination with chemotherapy, significantly decreases primary tumor progression, reduces metastasis, and improves survival by CD8+ T-cell-dependent mechanisms, thus indicating that the immune microenvironment of tumors can be reprogrammed to instead foster antitumor immunity and improve response to cytotoxic therapy.
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Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance
Kari R. Fischer,Anna Durrans,Sharrell Lee,Jianting Sheng,Fuhai Li,Stephen T. C. Wong,Hyejin Choi,Tina El Rayes,Seongho Ryu,Seongho Ryu,Juliane S. Troeger,Robert F. Schwabe,Linda T. Vahdat,Nasser K. Altorki,Vivek Mittal,Dingcheng Gao +15 more
TL;DR: The potential of an EMT-targeting strategy, in conjunction with conventional chemotherapies, for breast cancer treatment is suggested, using a mesenchymal-specific Cre-mediated fluorescent marker switch system in spontaneous breast-to-lung metastasis models.
References
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