Role of matrix metalloproteinases and their inhibitors in the development of cervical metastases in papillary thyroid cancer

Bumber, Boris; Kavanagh, Marcel Marjanović; Jakovčević, Antonia; Sinčić, Nino; Prstačić, Ratko; Prgomet, Drago

doi:10.1111/coa.13466

Cited by 26 publications

(31 citation statements)

References 23 publications

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“…There is also a lack of effective and specific prognostic molecular markers for PTC. 17 The relationship between MMPs and tumors is a current hotspot of modern cancer research. MMPs play important roles in pathophysiological processes, such as the dynamic extracellular matrix balance, as well as in tissue remodeling and repair.…”

Section: Discussionmentioning

confidence: 99%

Clinical value of matrix metalloproteinase-2 and -9 in ultrasound-guided radiofrequency ablation treatment for papillary thyroid carcinoma

2020

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Objective This study aimed to investigate serum matrix metalloproteinase (MMP)-2 and MMP-9 levels in patients with papillary thyroid carcinoma (PTC). Methods Forty-one patients with PTC undergoing ultrasound-guided radiofrequency ablation (RFA) and 56 controls were included. Serum MMP-2 and MMP-9 levels were determined by enzyme-linked immunosorbent assay before and after surgery. Potential affecting factors were evaluated by logistic regression analysis. Results Serum MMP-2 and MMP-9 levels were significantly higher in PTC patients compared with controls, and decreased significantly after surgery. According to receiver operating characteristic curve analysis, diagnostic values for preoperative serum MMP-2 and MMP-9 levels were 82.4% and 86.6%. There was no contrast-agent perfusion in the ablation zone in 88.5% of lesions, and enhancement within or at the lesion edge in 11.4%. The volume reduction at 3 months’ follow-up was >40%. Age, microcalcification, irregular shape, and lesion diameter and number were influencing factors for PTC. Age, and lesion diameter and number were independent risk factors, while calcification and morphology were protective factors. Conclusion Serum MMP-2 and MMP-9 levels have important clinical values for the diagnosis and treatment of PTC by RFA. Preoperative serum MMP-2 and MMP-9 levels, combined with other affecting factors, contribute to disease prognosis.

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Section: Discussionmentioning

confidence: 99%

Clinical value of matrix metalloproteinase-2 and -9 in ultrasound-guided radiofrequency ablation treatment for papillary thyroid carcinoma

2020

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“…Moreover, we provide evidence that MMP1 is a crucial downstream target gene of ETV4 in PTC through the ChIP assays. MMP1 has been reported to function as an oncogene in various cancer types (20), including thyroid cancer (25)(26)(27)(28). Notably, most MMP genes possess ETS binding elements in their promoter (29).…”

Section: Discussionmentioning

confidence: 99%

CRLF1–MYH9 Interaction Regulates Proliferation and Metastasis of Papillary Thyroid Carcinoma Through the ERK/ETV4 Axis

Sun

et al. 2020

Front. Endocrinol.

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In our previous study, we have shown that CRLF1 can promote proliferation and metastasis of papillary thyroid carcinoma (PTC); however, the mechanism is unclear. Herein, we investigated whether the interaction of CRLF1 and MYH9 regulates proliferation and metastasis of PTC cells via the ERK/ETV4 axis. Immunohistochemistry (IHC), qPCR, and Western blotting assays were performed on PTC cells and normal thyroid cells to profile specific target genes. In vitro assays and in vivo assays were also conducted to examine the molecular mechanism. Results showed that CRLF1 directly bound MYH9 to enhance the stability of CRLF1 protein. Inhibition of MYH9 in PTC cells overexpressing CRLF1 significantly reversed malignant phenotypes, and CRLF1 overexpression activated ERK pathway, in vitro, and in vivo. RNA-sequencing revealed that ETV4 is a downstream target gene of CRLF1, which was up-regulated following ERK activation. Moreover, it was revealed that ETV4 is highly expressed in PTC tissues and is associated with poor prognosis. Finally, the ChIP assays showed that ETV4 induces the expression of matrix metalloproteinase 1 (MMP1) by binding to its promoter on PTC cells. Altogether, our study demonstrates that CRLF1 interacts with MYH9, promoting cell proliferation and metastasis via the ERK/ETV4 axis in PTC.

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“…The ratio of MMP-2 to TIMP-2 expression is a prognostic factor for surgically treated MTC, and both of these metalloproteinases play a role in PTC [ 136 , 137 , 138 ]. MMP-9 expression is upregulated in PTC and might be a prognostic indicator for more advanced-stage cancer [ 139 , 140 , 141 , 142 ]. The prognostic role of other components of the extracellular matrix of thyroid cancer tangentially involved in angiogenetic processes, such as macrophages and T lymphocytes, is yet to be clarified [ 15 ].…”

Section: Angiogenesis and Prognosismentioning

confidence: 99%

Prognostic and Therapeutic Role of Angiogenic Microenvironment in Thyroid Cancer

Melaccio

Sgaramella

Pasculli

et al. 2021

Cancers

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Thyroid cancer is the most common endocrine malignancy, with a typically favorable prognosis following standard treatments, such as surgical resection and radioiodine therapy. A subset of thyroid cancers progress to refractory/metastatic disease. Understanding how the tumor microenvironment is transformed into an angiogenic microenvironment has a role of primary importance in the aggressive behavior of these neoplasms. During tumor growth and progression, angiogenesis represents a deregulated biological process, and the angiogenic switch, characterized by the formation of new vessels, induces tumor cell proliferation, local invasion, and hematogenous metastases. This evidence has propelled the scientific community’s effort to study a number of molecular pathways (proliferation, cell cycle control, and angiogenic processes), identifying mediators that may represent viable targets for new anticancer treatments. Herein, we sought to review angiogenesis in thyroid cancer and the potential role of proangiogenic cytokines for risk stratification of patients. We also present the current status of treatment of advanced differentiated, medullary, and poorly differentiated thyroid cancers with multiple tyrosine kinase inhibitors, based on the rationale of angiogenesis as a potential therapeutic target.

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Role of matrix metalloproteinases and their inhibitors in the development of cervical metastases in papillary thyroid cancer

Cited by 26 publications

References 23 publications

Clinical value of matrix metalloproteinase-2 and -9 in ultrasound-guided radiofrequency ablation treatment for papillary thyroid carcinoma

Clinical value of matrix metalloproteinase-2 and -9 in ultrasound-guided radiofrequency ablation treatment for papillary thyroid carcinoma

CRLF1–MYH9 Interaction Regulates Proliferation and Metastasis of Papillary Thyroid Carcinoma Through the ERK/ETV4 Axis

Prognostic and Therapeutic Role of Angiogenic Microenvironment in Thyroid Cancer

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