Advances in targeting the transforming growth factor β1 signaling pathway in lung cancer radiotherapy (Review)

Lu, Zhonghua; Tang, Yiting; Luo, Judong; Zhang, Shuyu; Zhou, Xifa; Fu, Lei

doi:10.3892/ol.2017.6991

Cited by 6 publications

(6 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We now show an induction of EMT and significant changes in EMT-related genes (suppression of mRNA expression of E-Cad, upregulation of mRNA expression of mesenchymal genes such as VIM, N-Cad, SLUG and SNAIL) by the knock down of TIMP-2 by siRNA in T2-KD OVCAR5 cells and in the gRNA2 cells. We also show that the EMT phenomenon in T2-KD and gRNA2 ovarian cancer cells may be mediated by a significant upregulation of TGFβ1 expression [ 45 ]. However, when TIMP-2 protein levels were suppressed in the gRNA1 cells, there was no significant increase in the level of TGFb1 expression but instead, a significant mRNA upregulation of EMT-associated TWIST1 was observed which was non-existent in gRNA2 cell line.…”

Section: Discussionmentioning

confidence: 99%

Knock down of TIMP-2 by siRNA and CRISPR/Cas9 mediates diverse cellular reprogramming of metastasis and chemosensitivity in ovarian cancer

Escalona

Chu

Kadife³

et al. 2022

Cancer Cell Int

View full text Add to dashboard Cite

Background The endogenous tissue inhibitor of metalloproteinase-2 (TIMP-2), through its homeostatic action on certain metalloproteinases, plays a vital role in remodelling extracellular matrix (ECM) to facilitate cancer progression. This study investigated the role of TIMP-2 in an ovarian cancer cell line in which the expression of TIMP-2 was reduced by either siRNA or CRISPR/Cas9. Methods OVCAR5 cells were transiently and stably transfected with either single or pooled TIMP-2 siRNAs (T2-KD cells) or by CRISPR/Cas9 under the influence of two distinct guide RNAs (gRNA1 and gRNA2 cell lines). The expression of different genes was analysed at the mRNA level by quantitative real time PCR (qRT-PCR) and at the protein level by immunofluorescence (IF) and western blot. Proliferation of cells was investigated by 5-Ethynyl-2′-deoxyuridine (EdU) assay or staining with Ki67. Cell migration/invasion was determined by xCELLigence. Cell growth in vitro was determined by 3D spheroid cultures and in vivo by a mouse xenograft model. Results Approximately 70–90% knock down of TIMP-2 expression were confirmed in T2-KD, gRNA1 and gRNA2 OVCAR5 ovarian cancer cells at the protein level. T2-KD, gRNA1 and gRNA2 cells exhibited a significant downregulation of MMP-2 expression, but concurrently a significant upregulation in the expression of membrane bound MMP-14 compared to control and parental cells. Enhanced proliferation and invasion were exhibited in all TIMP-2 knocked down cells but differences in sensitivity to paclitaxel (PTX) treatment were observed, with T2-KD cells and gRNA2 cell line being sensitive, while the gRNA1 cell line was resistant to PTX treatment. In addition, significant differences in the growth of gRNA1 and gRNA2 cell lines were observed in in vitro 3D cultures as well as in an in vivo mouse xenograft model. Conclusions Our results suggest that the inhibition of TIMP-2 by siRNA and CRISPR/Cas-9 modulate the expression of MMP-2 and MMP-14 and reprogram ovarian cancer cells to facilitate proliferation and invasion. Distinct disparities in in vitro chemosensitivity and growth in 3D culture, and differences in tumour burden and invasion to proximal organs in a mouse model imply that selective suppression of TIMP-2 expression by siRNA or CRISPR/Cas-9 alters important aspects of metastasis and chemosensitivity in ovarian cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Knock down of TIMP-2 by siRNA and CRISPR/Cas9 mediates diverse cellular reprogramming of metastasis and chemosensitivity in ovarian cancer

Escalona

Chu

Kadife³

et al. 2022

Cancer Cell Int

View full text Add to dashboard Cite

show abstract

“…40 Current strategies targeting the TGFB1 pathway in the prediction of radiation pneumonitis and the TGFB1 pathway in lung cancer radiotherapy may provide potential targets for lung cancer therapy. 41 Radiopharmaceutical or radioactive tracers: Radioactive substances, so-called radionuclides (radiopharmaceuticals or radiotracers), are absorbed by body tissues. However, they exhibit long-term toxicity and reduced excretion from the body.…”

Section: Dose Determinationmentioning

confidence: 99%

Radiation induced therapeutic effects in cancerous and tumor cells: A review

Upadhyay¹,

Rai²

2023

JSRT

View full text Add to dashboard Cite

Present review article describes use of radiation and radionuclides on cancer and cancer cell therapeutics. It also sketches out cumulative effects of radiation exposure received by the patients during cancer diagnostics. Though, in cancer therapeutics a selected and permissible dose is provided in several cycles to ablate the neoplastic cells and improve the condition of patient, but radiation harms surrounding cells and imparts negative effects on biology of cells. Ionizing radiation (IR) promotes cancer cell death through cytotoxicity. This article emphasizes both remedial effects and biological effects of radiation and radio-resistance in cells. It suggests safe use of radionucleides by encapsulating them in nanomaterials so as to use it alternate to chemotherapy to destroy various cancer types to enhance the survival of normal cells. This article explains effect of ionizing and non-ionizing radiation on cellular metabolism and genetics.

show abstract

“…The TGFβ family is a group of pleiotropic growth factors (TGFβ isoforms, anti-Mullerian hormone, bone morphogenic proteins—BMPs) that activate the signal transduction cascade involved in carcinogenesis and tumor progression. These cytokines are a master regulator of lung development, inflammation, and injury-repair processes, and their role depends largely on their expression [ 10 , 39 ]. In mammalians, there are three isoforms present—TGFβ1, TGFβ2, and TGFβ3, all of which activate the same receptors and share some functions [ 40 ].…”

Section: Promising Circulating Biomarkers In Radiotherapy Monitorimentioning

confidence: 99%

“…TGFβ1 was reported as one of the most important growth factors among the molecules expressed in tissues following IR exposure. TGFβ1 is also associated with the incidence of RP and may serve as a sensitive marker of fibrinolytic changes that stimulate the differentiation of fibroblasts into myofibroblasts [ 10 , 39 , 43 , 44 ]. Myofibroblasts drive the cycle of increased epithelial injury (especially alveolar type II cells) and boost collagen synthesis.…”

Section: Promising Circulating Biomarkers In Radiotherapy Monitorimentioning

confidence: 99%

“…RT should be provided for all patients with stage III NSCLC and in patients with stage IV disease who may benefit from local therapy. Uses of RT for NSCLC include (1) definitive therapy for locally advanced NSCLC, generally combined with chemotherapy; (2) definitive therapy in patients with early-stage disease, who are medically inoperable, who refuse surgery, or who are high-risk surgical candidates; (3) preoperative or postoperative therapy for selected patients treated with surgery; (4) therapy for limited recurrences and metastases; and (5) palliative therapy for patients with incurable NSCLC [ 9 , 10 , 11 , 12 , 13 ]. The main restrictions of RT are tumor hypoxia, repopulation, DNA damage repair, and molecular mechanisms linked to RT resistance and treatment toxicity, manifesting in radiation-induced lung injury (RILI).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Markers Useful in Monitoring Radiation-Induced Lung Injury in Lung Cancer Patients: A Review

Śliwińska-Mossoń

Wadowska

Trembecki

et al. 2020

JPM

View full text Add to dashboard Cite

In 2018, lung cancer was the most common cancer and the most common cause of cancer death, accounting for a 1.76 million deaths. Radiotherapy (RT) is a widely used and effective non-surgical cancer treatment that induces remission in, and even cures, patients with lung cancer. However, RT faces some restrictions linked to the radioresistance and treatment toxicity, manifesting in radiation-induced lung injury (RILI). About 30–40% of lung cancer patients will develop RILI, which next to the local recurrence and distant metastasis is a substantial challenge to the successful management of lung cancer treatment. These data indicate an urgent need of looking for novel, precise biomarkers of individual response and risk of side effects in the course of RT. The aim of this review was to summarize both preclinical and clinical approaches in RILI monitoring that could be brought into clinical practice. Next to transforming growth factor-β1 (TGFβ1) that was reported as one of the most important growth factors expressed in the tissues after ionizing radiation (IR), there is a group of novel, potential biomarkers—microRNAs—that may be used as predictive biomarkers in therapy response and disease prognosis.

show abstract

Advances in targeting the transforming growth factor β1 signaling pathway in lung cancer radiotherapy (Review)

Cited by 6 publications

References 78 publications

Knock down of TIMP-2 by siRNA and CRISPR/Cas9 mediates diverse cellular reprogramming of metastasis and chemosensitivity in ovarian cancer

Knock down of TIMP-2 by siRNA and CRISPR/Cas9 mediates diverse cellular reprogramming of metastasis and chemosensitivity in ovarian cancer

Radiation induced therapeutic effects in cancerous and tumor cells: A review

Markers Useful in Monitoring Radiation-Induced Lung Injury in Lung Cancer Patients: A Review

Contact Info

Product

Resources

About