TGF-β in radiotherapy: Mechanisms of tumor resistance and normal tissues injury

Farhood, Bagher; Khodamoradi, Ehsan; Hoseini‐Ghahfarokhi, Mojtaba; Motevaseli, Elahe; Mirtavoos-Mahyari, Hanifeh; Musa, Ahmed Eleojo; Najafi, Masoud

doi:10.1016/j.phrs.2020.104745

Cited by 95 publications

(79 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, ALK1 as a TGF-β type I receptor, plays a key role in non-canonical pathway of TGF-β and is expressed in chondrocytes, endothelial cells and so on. Upon TGF-β attachment, ALK1 is induced to form a complex with ALK5, resulting in Smad1/5 activation (Finnson et al, 2008;Finnson et al, 2010;Pardali et al, 2010;van der Kraan et al, 2010;Farhood et al, 2020), and suppressing ALK5-Smad2/3 signaling (Finnson et al, 2008). The mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K) and Rho-like GTPase contribute to non-canonical pathway of TGF-β ( Figure 2) (Derynck and Zhang, 2003;Moustakas and Heldin, 2005;Zhang, 2009).…”

Section: Non-canonical Pathwaymentioning

confidence: 99%

Toward Regulatory Effects of Curcumin on Transforming Growth Factor-Beta Across Different Diseases: A Review

et al. 2020

Self Cite

View full text Add to dashboard Cite

Immune response, proliferation, migration and angiogenesis are juts a few of cellular events that are regulated by transforming growth factor-β (TGF-β) in cells. A number of studies have documented that TGF-β undergoes abnormal expression in different diseases, e.g., diabetes, cancer, fibrosis, asthma, arthritis, among others. This has led to great fascination into this signaling pathway and developing agents with modulatory impact on TGF-β. Curcumin, a natural-based compound, is obtained from rhizome and roots of turmeric plant. It has a number of pharmacological activities including antioxidant, anti-inflammatory, anti-tumor, anti-diabetes and so on. Noteworthy, it has been demonstrated that curcumin affects different molecular signaling pathways such as Wnt/β-catenin, Nrf2, AMPK, mitogen-activated protein kinase and so on. In the present review, we evaluate the potential of curcumin in regulation of TGF-β signaling pathway to corelate it with therapeutic impacts of curcumin. By modulation of TGF-β (both upregulation and down-regulation), curcumin ameliorates fibrosis, neurological disorders, liver disease, diabetes and asthma. Besides, curcumin targets TGF-β signaling pathway which is capable of suppressing proliferation of tumor cells and invading cancer cells.

show abstract

Section: Non-canonical Pathwaymentioning

confidence: 99%

Toward Regulatory Effects of Curcumin on Transforming Growth Factor-Beta Across Different Diseases: A Review

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…TGF-β is usually secreted in the form of inactivation in the extracellular matrix and is released from the latency-related peptide (LAP) by external stimuli such as radiation. Besides, the production of reactive oxygen species (ROS) after radiation can also promote the release of TGF-β, thus increasing the immunosuppressive effect (25). Similarly, IL-10, an important immunosuppressive factor, induces an immunosuppressive pathway by promoting S100A9 nuclear localization and MDSC maturation (55).…”

Section: Discussionmentioning

confidence: 99%

“…The change of tumor immunogenicity induced by radiation is an essential mechanism for improving tumor microenvironment (TME) and immune synergism (23). Among them, HMGB1, TGB-β, and IL-10 are important cytokines in radiation-induced ICD and then participate in the process of immune regulation (24)(25)(26). As one of the criticalcrucial DAMPs, HMGB1 plays an essential role in the immune effect stage (27).…”

Section: Introductionmentioning

confidence: 99%

Irradiation-Induced Changes in the Immunogenicity of Lung Cancer Cell Lines: Based on Comparison of X-rays and Carbon Ions

Ran

Wang

Dai

et al. 2021

Front. Public Health

View full text Add to dashboard Cite

Increasing the immunogenicity of tumors is considered to be an effective means to improve the synergistic immune effect of radiotherapy. Carbon ions have become ideal radiation for combined immunotherapy due to their particular radiobiological advantages. However, the difference in time and dose of immunogenic changes induced by Carbon ions and X-rays has not yet been fully clarified. To further explore the immunogenicity differences between carbon ions and X-rays induced by radiation in different “time windows” and “dose windows.” In this study, we used principal component analysis (PCA) to screen out the marker genes from the single-cell RNA-sequencing (scRNA-seq) of CD8+ T cells and constructed a protein-protein interaction (PPI) network. Also, ELISA was used to test the exposure levels of HMGB1, IL-10, and TGF-β under different “time windows” and “dose windows” of irradiation with X-rays and carbon ions for A549, H520, and Lewis Lung Carcinoma (LLC) cell lines. The results demonstrated that different marker genes were involved in different processes of immune effect. HMGB1 was significantly enriched in the activated state, while the immunosuppressive factors TGF-β and IL-10 were mainly enriched in the non-functional state. Both X-rays and Carbon ions promoted the exposure of HMGB1, IL-10, and TGF-β in a time-dependent manner. X-rays but not Carbon ions increased the HMGB1 exposure level in a dose-dependent manner. Besides, compared with X-rays, carbon ions increased the exposure of HMGB1 while relatively reduced the exposure levels of immunosuppressive factors IL-10 and TGF-β. Therefore, we speculate that Carbon ions may be more advantageous than conventional X-rays in inducing immune effects.

show abstract

“…Experimental animals. [6][7][8] week old male C57BL/6J mice, obtained from Jackson Laboratories, were used in this study. The mice were housed at the University of Nebraska Medical Center (UNMC) and exposed to a 12 h light/12 h dark cycle and fed and watered ad libitum.…”

Section: Methodsmentioning

confidence: 99%

Adipocytes protect fibroblasts from radiation-induced damage by adiponectin secretion

Kosmacek

Oberley‐Deegan

2020

Sci Rep

View full text Add to dashboard Cite

Prostate and colon cancers are among the most common cancers diagnosed annually, and both often require treatment with radiation therapy. Advancement in radiation delivery techniques has led to highly accurate targeting of tumor and sparing of normal tissue; however, in the pelvic region it is anatomically difficult to avoid off-target radiation exposure to other organs. Chronically the effects of normal urogenital tissue exposure can lead to urinary frequency, urinary incontinence, proctitis, and erectile dysfunction. Most of these symptoms are caused by radiation-induced fibrosis and reduce the quality of life for cancer survivors. We have observed in animal models that the severity of radiation-induced fibrosis in normal tissue correlates to damaged fat reservoirs in the pelvic region. We hypothesize that adipocytes may secrete a factor that prevents the induction of radiation-associated fibrosis in normal tissues. In these studies we show that the adipokine, adiponectin, is secreted by primary mouse adipocytes and protects fibroblasts from radiation-induced cell death, myofibroblast formation, and senescence. Further, we demonstrated that adiponectin does not protect colorectal or prostate cancer cells from radiation-induced death. Thus, we propose that adiponectin, or its downstream pathway, would provide a novel target for adjuvant therapy when treating pelvic cancers with radiation therapy. Radiation is used to treat a variety of pelvic cancers, including prostate and colorectal cancers. While radiation is an effective tool to treat these cancers, radiation also damages surrounding normal tissues. The chronic side effects of radiation treatment are similar for either prostate or colorectal cancer and include: urinary frequency, urinary incontinence, proctitis, erectile dysfunction, and bowel fibrosis 1-4. Most of these long-term side-effects are due to radiation-induced fibrosis. Fibroblasts are the cell type that is most studied in the context of radiation-induced fibrosis. In particular, fibroblasts, which function to maintain normal extracellular matrix (ECM) by producing proteins such as collagen and fibronectin, can become chronically activated after radiation exposure 5. Activated fibroblasts, or myofibroblasts, are initiated by ionizing radiation that activates the TGFβ pathway and chronic production of reactive oxygen species (ROS), which ultimately produces aberrant amounts of ECM 6-8. Irradiation of fibroblasts in normal tissue can lead to cell death, fibroblast activation, or cellular senescence, all of which can produce long term side effects including inflammation, fibrosis, and chronic tissue dysfunction 5,9. There are other cell types involved in fibrosis besides fibroblasts. Immune cells can provide a pro-fibrotic niche to activate fibroblasts and cause epithelial to mesenchymal transformation 10-12. Additionally, the pelvic region contains a large depot of visceral and subcutaneous adipose tissue. The role of adipocytes in radiationinduced fibrosis is unknown. Previously we have published ...

show abstract

TGF-β in radiotherapy: Mechanisms of tumor resistance and normal tissues injury

Cited by 95 publications

References 86 publications

Toward Regulatory Effects of Curcumin on Transforming Growth Factor-Beta Across Different Diseases: A Review

Toward Regulatory Effects of Curcumin on Transforming Growth Factor-Beta Across Different Diseases: A Review

Irradiation-Induced Changes in the Immunogenicity of Lung Cancer Cell Lines: Based on Comparison of X-rays and Carbon Ions

Adipocytes protect fibroblasts from radiation-induced damage by adiponectin secretion

Contact Info

Product

Resources

About