scholarly journals Inhibition of Transforming Growth Factor-β Activation Diminishes Tumor Progression and Osteolytic Bone Disease in Mouse Models of Multiple Myeloma

2016 ◽  
Vol 186 (3) ◽  
pp. 678-690 ◽  
Author(s):  
Ailing Lu ◽  
Manuel A. Pallero ◽  
Weiqi Lei ◽  
Huixian Hong ◽  
Yang Yang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Growth Factor ◽  
Tumor Progression ◽  
Mouse Models ◽  
Bone Disease ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Osteolytic Bone Disease

scholarly journals Mouse models of transforming growth factor β impact in breast development and cancer

2005 ◽  
Vol 12 (4) ◽  
pp. 749-760 ◽  
Author(s):  
R Serra ◽  
M R Crowley
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Tumor Progression ◽  
Mouse Models ◽  
Transforming Growth Factor ◽  
Normal Development ◽  
Transforming Growth Factor Β ◽  
Branching Morphogenesis ◽  
Breast Development ◽  
Normal Mammary Gland

It is now recognized that transforming growth factor β (TGF-β) is an important factor that regulates normal breast development as well as breast cancer. Genetically engineered mouse models have been used to determine the role and mechanism of TGF-β action in normal development and diseases of the breast. Using these models, it has been determined that TGF-β regulates many steps of normal mammary gland development including branching morphogenesis, functional differentiation, cell-lineage decisions, and involution. Effects of TGF-β on normal development are mediated through signaling in both the epithelial and stromal compartments. In cancer, mouse models have indicated that TGF-β has biphasic effects on tumor progression, acting as a tumor suppressor in early stages of cancer and promoting invasion and metastasis at later stages. In addition, TGF-β may play a role in tumor progression through effects on the microenvironment. Recently, experiments in several mouse models have suggested that antagonism of TGF-β signaling may provide a therapeutic target for late-stage breast cancer, blocking metastasis without detrimental side effects. In the future, genetically altered mice will be used to establish models of human breast disease providing opportunities to test strategies for disease prevention and treatment.

127 TREATMENTS WITH DIVERSE ENDOCRINE-DISRUPTING CHEMICALS RESULTED IN THE INHIBITION OF OVARIAN TUMOR PROGRESSION VIA INTERRUPTION OF TRANSFORMING GROWTH FACTOR-β IN IN VITRO AND XENOGRAFTED MOUSE MODELS

2014 ◽  
Vol 26 (1) ◽  
pp. 177
Author(s):  
H.-R. Lee ◽  
R.-E. Go ◽  
K.-C. Choi
Keyword(s):  
Ovarian Cancer ◽  
Growth Factor ◽  
Mouse Model ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Mouse Models ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Xenograft Mouse Model

Activated oestrogen receptor (ER) signaling pathway by 17β-estadiol (E2) appeared to suppress transforming growth factor β (TGF-β) signaling pathway by cross-talk with TGF-β components in ER-positive cancer cells. In this study, we further examined the inhibitory effects of alkylphenols, including 4-nonylphenol (NP), 4-otylphenol (OP), bisphenol A (BPA), and benzophenon-1 (BP-1), in TGF-β signaling pathway. The transcriptional and translational levels of TGF-β-related genes were examined by reverse-transcription PCR (RT-PCR), Western blotting analysis in xenografted mouse models of ovarian cancer BG-1 cells. The NP, OP, and BPA induced the expression of snoN, a TGF-β pathway inhibitor. Treatment with NP, BPA, and BP-1 resulted in decreased phosphorylation of Smad3, a downstream target of TGF-β. With these 2 effects, NP and BPA stimulated the proliferation of BG-1 cells via inhibition of the TGF-β signaling pathway. In a xenograft mouse model, transplanted BG-1 ovarian cancer cells showed significantly decreased phosphorylation of Smad3 and increased expression of snoN in the ovarian tumour masses following treatment with E2, NP, or BPA. In parallel with an in vitro model, the expressions of TGF-β signaling pathway were similarly regulated by NP or BPA in a xenograft mouse model, revealing consistent results. Taken together, these results support that NP and BPA may cause the disruption of the TGF-β signaling pathway and increase the risk of oestrogen-dependent cancers such as ovarian cancer. This work was supported by a grant from the Next-Generation BioGreen 21 Program (No. PJ009599), Rural Development Administration, Republic of Korea.

scholarly journals Human Colorectal Cancer from the Perspective of Mouse Models

Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 788 ◽  
Author(s):  
Monika Stastna ◽  
Lucie Janeckova ◽  
Dusan Hrckulak ◽  
Vitezslav Kriz ◽  
Vladimir Korinek
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Mouse Models ◽  
Intracellular Signaling ◽  
Transforming Growth Factor ◽  
Molecular Subtype ◽  
Transforming Growth Factor Β ◽  
Dna Mismatch ◽  
Individual Mouse ◽  
Consensus Molecular Subtype

Colorectal cancer (CRC) is a heterogeneous disease that includes both hereditary and sporadic types of tumors. Tumor initiation and growth is driven by mutational or epigenetic changes that alter the function or expression of multiple genes. The genes predominantly encode components of various intracellular signaling cascades. In this review, we present mouse intestinal cancer models that include alterations in the Wnt, Hippo, p53, epidermal growth factor (EGF), and transforming growth factor β (TGFβ) pathways; models of impaired DNA mismatch repair and chemically induced tumorigenesis are included. Based on their molecular biology characteristics and mutational and epigenetic status, human colorectal carcinomas were divided into four so-called consensus molecular subtype (CMS) groups. It was shown subsequently that the CMS classification system could be applied to various cell lines derived from intestinal tumors and tumor-derived organoids. Although the CMS system facilitates characterization of human CRC, individual mouse models were not assigned to some of the CMS groups. Thus, we also indicate the possible assignment of described animal models to the CMS group. This might be helpful for selection of a suitable mouse strain to study a particular type of CRC.

scholarly journals Targeting all transforming growth factor-β isoforms with an Fc chimeric receptor impairs tumor growth and angiogenesis of oral squamous cell cancer

2020 ◽  
Vol 295 (36) ◽  
pp. 12559-12572
Author(s):  
Kazuki Takahashi ◽  
Yuichi Akatsu ◽  
Katarzyna A. Podyma-Inoue ◽  
Takehisa Matsumoto ◽  
Hitomi Takahashi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Oral Cancer ◽  
Tumor Growth ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Type I ◽  
Oral Cancer Cells ◽  
Tgf Β1

Tumor progression is governed by various growth factors and cytokines in the tumor microenvironment (TME). Among these, transforming growth factor-β (TGF-β) is secreted by various cell types residing in the TME and promotes tumor progression by inducing the epithelial-to-mesenchymal transition (EMT) of cancer cells and tumor angiogenesis. TGF-β comprises three isoforms, TGF-β1, -β2, and -β3, and transduces intracellular signals via TGF-β type I receptor (TβRI) and TGF-β type II receptor (TβRII). For the purpose of designing ligand traps that reduce oncogenic signaling in the TME, chimeric proteins comprising the ligand-interacting ectodomains of receptors fused with the Fc portion of immunoglobulin are often used. For example, chimeric soluble TβRII (TβRII-Fc) has been developed as an effective therapeutic strategy for targeting TGF-β ligands, but several lines of evidence indicate that TβRII-Fc more effectively traps TGF-β1 and TGF-β3 than TGF-β2, whose expression is elevated in multiple cancer types. In the present study, we developed a chimeric TGF-β receptor containing both TβRI and TβRII (TβRI-TβRII-Fc) and found that TβRI-TβRII-Fc trapped all TGF-β isoforms, leading to inhibition of both the TGF-β signal and TGF-β–induced EMT of oral cancer cells, whereas TβRII-Fc failed to trap TGF-β2. Furthermore, we found that TβRI-TβRII-Fc suppresses tumor growth and angiogenesis more effectively than TβRII-Fc in a subcutaneous xenograft model of oral cancer cells with high TGF-β expression. These results suggest that TβRI-TβRII-Fc may be a promising tool for targeting all TGF-β isoforms in the TME.

Sign in / Sign up

Export Citation Format

Share Document