Mimicking the breast metastatic microenvironment: characterization of a novel syngeneic model of HER2 + breast cancer.
Autor: | Baugh AG; Department of Medicine, Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Gonzalez E; Department of Medicine, Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Narumi VH; Department of Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Kreger J; Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA, USA., Liu Y; Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA, USA., Rafie C; University of Miami Miller School of Medicine, Miami, FL, USA., Castanon S; Department of Medicine, Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Jang J; Department of Medicine, Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Kagohara LT; Johns Hopkins Bloomberg Kimmel Institute for Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Johns Hopkins Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA., Anastasiadou DP; Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.; Tumor Microenvironment & Metastasis Program, Montefiore-Einstein Cancer Center, Bronx, NY, USA., Leatherman J; Johns Hopkins Bloomberg Kimmel Institute for Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA., Armstrong TD; Johns Hopkins Bloomberg Kimmel Institute for Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Johns Hopkins Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA., Chan I; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA., Karagiannis GS; Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.; Tumor Microenvironment & Metastasis Program, Montefiore-Einstein Cancer Center, Bronx, NY, USA.; Integrated Imaging Program for Cancer Research, Albert Einstein College of Medicine, Bronx, NY, USA.; Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, NY, USA.; Cancer Dormancy and Tumor Microenvironment Institute, Albert Einstein College of Medicine, Bronx, NY, USA., Jaffee EM; Johns Hopkins Bloomberg Kimmel Institute for Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Johns Hopkins Convergence Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA., MacLean A; Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA, USA., Roussos Torres ET; Department of Medicine, Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. |
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Jazyk: | angličtina |
Zdroj: | BioRxiv : the preprint server for biology [bioRxiv] 2024 Jan 30. Date of Electronic Publication: 2024 Jan 30. |
DOI: | 10.1101/2024.01.25.577282 |
Abstrakt: | Preclinical murine models in which primary tumors spontaneously metastasize to distant organs are valuable tools to study metastatic progression and novel cancer treatment combinations. Here, we characterize a novel syngeneic murine breast tumor cell line, NT2.5-lung metastasis (-LM), that provides a model of spontaneously metastatic neu-expressing breast cancer with quicker onset of widespread metastases after orthotopic mammary implantation in immune-competent NeuN mice. Within one week of orthotopic implantation of NT2.5-LM in NeuN mice, distant metastases can be observed in the lungs. Within four weeks, metastases are also observed in the bones, spleen, colon, and liver. Metastases are rapidly growing, proliferative, and responsive to HER2-directed therapy. We demonstrate altered expression of markers of epithelial-to-mesenchymal transition (EMT) and enrichment in EMT-regulating pathways, suggestive of their enhanced metastatic potential. The new NT2.5-LM model provides more rapid and spontaneous development of widespread metastases. Besides investigating mechanisms of metastatic progression, this new model may be used for the rationalized development of novel therapeutic interventions and assessment of therapeutic responses targeting distant visceral metastases. Competing Interests: Competing interests: EMJ is a paid consultant for Adaptive Biotech, CSTONE, Achilles, DragonFly, and Genocea. She receives funding from Lustgarten Foundation and Bristol Myer Squibb. She is the Chief Medical Advisor for Lustgarten and SAB advisor to the Parker Institute for Cancer Immunotherapy (PICI) and for the C3 Cancer Institute. |
Databáze: | MEDLINE |
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