Attenuation of TGF-β signaling supports tumor progression of a mesenchymal-like mammary tumor cell line in a syngeneic murine model
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Previous studies have suggested that TGF-β functions as a tumor promoter in metastatic, mesenchymal-like breast cancer cells and that TGF-β inhibitors can effectively abrogate tumor progression in several of these models. Here we report a novel observation with the use of genetic and pharmacological approaches, and murine mammary cell injection models in both syngeneic and immune compromised mice. We found that TGF-β receptor II (TβRII) knockdown in the MMTV-PyMT derived Py8119, a mesenchymal-like murine mammary tumor cell line, resulted in increased orthotopic tumor growth potential in a syngeneic background and a similar trend in an immune compromised background. Systemic treatment with a small-molecule TGF-β receptor I kinase inhibitor induced a trend towards increased metastatic colonization of distant organs following intracardiac inoculation of Py8119 cells, with little effect on the colonization of luminal-like Py230 cells, also derived from MMTV-PyMT tumors. Taken together, our data suggest that the attenuation of TGF-β signaling in mesenchymal-like mammary tumors does not necessarily inhibit their malignant potential, and anti-TGF-β therapeutic intervention requires greater precision in identifying molecular markers in tumors with an indication of functional TGF-β signaling.
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Treatment with a pan-TGF-β antibody increased cancer dissemination in three of twelve syngeneic mouse mammary carcinoma models.
“and increased cancer dissemination in another three332.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [332]
Treatment with a pan-TGF-β antibody reduced metastasis in only three of twelve syngeneic mouse mammary carcinoma models.
“Additionally, treatment with a pan-TGF-β antibody reduced metastasis in only three of twelve syngeneic mouse mammary carcinoma models”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [332]
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Macrophage PPARγ inhibits Gpr132 to mediate the anti-tumor effects of rosiglitazone
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“The Py230 cell line was derived from spontaneous mam- mary tumors in C57BL/6 MMTV-PyMT female transgenic mice (RRID:CVCL_AQ08) (Biswas et al., 2014).”
BackgroundChung, H. Y., Lee, Y. S., Mayoral, R., Oh, D. Y., Siu, J., Webster, N. J. G., Sears, D. D., Olefsky, J. M., & Ellies, L. G. (2014) · Oncogene · doi:10.1038/onc.2014.283 · Cited by 57 · see citing works
Self-citationFam20C Regulates Bone Resorption and Breast Cancer Bone Metastasis through Osteopontin and BMP4
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“Py230 and Py8119 cells (19) were provided by Dr.”
MethodProteolysis-targeting chimera against BCL-XL destroys tumor-infiltrating regulatory T cells
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Multipotent luminal mammary cancer stem cells model tumor heterogeneity
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NR1D1 Stimulates Antitumor Immune Responses in Breast Cancer by Activating cGAS-STING Signaling
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“Control and Nr1d1 KO-Py230 cells were implanted into the mammary fat pads of Nr1d1 WT or KO C57BL/6 mice.”
InfluentialKatara, G. K., Kulshrestha, A., Mao, L., Wang, X., Sahoo, M., Ibrahim, S. A.-S., Pamarthy, S., Suzue, K., Shekhawat, G. S., Gilman‐Sachs, A., et al. (2017) · Molecular Oncology · doi:10.1002/1878-0261.12159 · Cited by 43 · see citing works
“Py230 cells are derived from MMTV-PyMT (mouse mammary tumor virus promoter-driven polyoma middle T-antigen) spontaneous tumor mouse and a well-established model for studying metastasis (Biswas et al., 2014).”
BackgroundDifferential regulation of breast cancer bone metastasis by PARP1 and PARP2
Zuo, H., Yang, D., Yang, Q., Tang, H., Fu, Y., & Wan, Y. (2020) · Nature Communications · doi:10.1038/s41467-020-15429-z · Cited by 43 · see citing works
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Mammary Gland Involution Provides a Unique Model to Study the TGF-β Cancer Paradox
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“In normal epithelium, key tumor suppressive capacities of TGF-β include inhibiting normal epithelial cell proliferation and inducing apoptosis [3], functions thought to be required for blocking progression of initiated cancer cells [13].”
BackgroundLipid Osteoclastokines Regulate Breast Cancer Bone Metastasis
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Inhibition of myeloid PD-L1 suppresses osteoclastogenesis and cancer bone metastasis
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“The luciferase-labeled Py8119 bonemetastatic-prone mouse mammary tumor cell line [38] originally derived from spontaneous mammary tumors in C57BL/6 MMTV-PyMT female transgenic mice [39] was provided by Dr.”
MethodEstablishment and characterization of a C57BL/6 mouse model of bone metastasis of breast cancer
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“These studies employed cell lines, Py8119 [7] and PyMT-BO1 [8], obtained from spontaneously arising tumors in mouse mammary tumor virus promoter-driven Polyoma middle T-antigen (MMTV-PyMT) transgenic C57BL/6 mice.”
BackgroundMethodInfluentialAge-associated genes in human mammary gland drive human breast cancer progression
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“taining protease inhibitors and processed as described previously [6].”
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“One possible explanation for this is the direct effect that TGF-β blockade has on cancer cells, given that the loss of TGF-β signalling promotes mesenchymal–epithelial transition—an important step during metastasis [37].”
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“Each of the 4 inguinal nipples of 16 albino C57BL/6 (Harlan Labs) mice were randomized such that each mouse had 2 mammary fat pads inoculated with 10(4) Py8119 mammary tumor cells [24] and the other 2 with an equal volume of saline.”
MethodNew insights into fibrotic signaling in renal cell carcinoma
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“Both cell lines are derived from MMTV-PyMT transgene-induced mammary tumors (17) (Figure S2C).”
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“The PyMT model of breast cancer has been previously used to study the microenvironmental influence on disease progression in an immunecompetent microenvironment [23].”
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The role of macrophage migratory behavior in development, homeostasis and tumor invasion
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“Finally, both RK20449 or acalisib, another PI3K p110 d inhibitor, produce striking reductions in orthotopic PyMT mammary tumor growth in vivo (Murrey et al., manuscript submitted) (129).”
Cytokines and cancer-associated fibroblasts
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“A limitation of our study is that the PyMT tumor-derived Py8119 cell model is orthotopic whereas spontaneous PyMT tumors arise from the mammary ductal epithelium (16, 42, 45).”
InfluentialSelf-citationAdvances in Immunotherapy for Intrahepatic Cholangiocarcinoma
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- Authors
- Biswas, T., Gu, X., Yang, J., Ellies, L. G., & Sun, L.-Z.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- University of California San Diego (US)
- Corresponding author
- Sun, Lu-Zhe
- Venue
- Cancer Letters
- Publisher
- Elsevier BV
- Published
- 2014-04
- Volume
- 346
- Issue
- 1
- Pages
- 129-138
- ISSN
- 0304-3835 (ISSN-L)
- PMC
- PMC3947668
- OpenAlex
- W2099541675
- Cited by
- 52
- References
- 68
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 7 · 2021: 6 · 2020: 5 · 2019: 1 · 2018: 5 · 2017: 3 · 2016: 4 · 2015: 3 · 2014: 2
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Cancer Letters (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- NIH (R01CA75253, R01CA79683)
- Cancer Therapy and Research Center at University of Texas Health Science Center at San Antonio (2P30CA054174-17)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- TGF-beta signaling, TGFBR2, tumor progression, metastasis, TGF-beta receptor I kinase inhibitor, syngeneic murine model, orthotopic tumor growth, anti-TGF-beta therapy, breast cancer cell lines
- MeSH terms
- Animals, Epithelial Cells, Female, Immunohistochemistry, Mammary Neoplasms, Experimental, Mesoderm, Mice, Inbred C57BL, Mice, Nude, Phenotype, Blotting, Western, Signal Transduction, Transforming Growth Factor beta, Disease Progression, Cell Line, Tumor, Protein Kinase Inhibitors, Mice, Real-Time Polymerase Chain Reaction
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