Abstract
BackgroundThe purpose of this study is to explore the role and mechanism of MMP-9 in the EMT process of thyroid cancer (TC), so as to provide a basis for clinical exploration of invasion and metastasis process of TC, looking for biological markers of tumor metastasis and molecular intervention therapy.MethodsWestern blot and RT-PCR were employed to detect the expression of MMP-9 in human normal thyroid cell line HT-ori3 and human TC cell lines IHH-4 (PTC), FTC-133, and 8505C. Expression levels of EMT-related markers: epithelial cell marker E-cadherin and stromal cell marker Vimentin in TGF-1-induced TC cell lines were detected by Western blot and RT-PCR, respectively. The effects of MMP-9 downregulation on cell invasion and metastasis were investigated by wound-healing assay and cell invasion experiment.ResultsThe protein and mRNA expression levels of MMP-9 in TC cell lines were increased compared with the human normal thyroid cell line HT-ori3. When TGF-β1 was added, the expression of EMT and Vimentin increased while the expression of E-cadherin decreased. Compared with the control group, the TC cells stably transfected with MMP-9 shRNA showed inhibited EMT, decreased Vimentin expression, and increased E-cadherin expression. The induction of TGF-β1 did not promote the occurrence of EMT in TC cells which were stably transformed with MMP-9 shRNA. The addition of TGF-β1 to TC cells increased the ability of the cells to migrate and invade. Compared with the control group, the migration and invasion ability of TC cells stably transfected with MMP-9 shRNA was significantly reduced, and the induction of TGF-β1 could not restore the migration and invasion ability of cells without MMP-9.ConclusionsIn conclusion, we found that MMP-9 can be used as a biomarker for TC, which can promote the EMT process of TGF-β1 induced TC, and thus affecting the cell migration and invasion ability.
Highlights
Thyroid cancer (TC) is one of the most common endocrine malignancies in the world, mainly derived from follicular cells [1]
Specific high expression of Matrix metalloproteinases (MMPs)-9 in thyroid cancer (TC) cell lines According to the results of Western blot and RT-PCR, the protein expression level (Fig. 1) and mRNA expression level (Fig. 2) of MMP-9 in TC cell lines IHH-4 (PTC), FTC-133, and 8505C were elevated compared with human normal thyroid cell line HT-ori3
MMP-9 altered the changes of epithelialmesenchymal transition (EMT)-related proteins in TC cells induced by Transforming growth factor (TGF)-β1 Western blot and RT-PCR experiments demonstrated that compared with control cells, the addition of TGFβ1 could promote cell EMT, increase the expression of Vimentin, and decrease the expression of E-cadherin
Summary
Thyroid cancer (TC) is one of the most common endocrine malignancies in the world, mainly derived from follicular cells [1]. Epithelial tumor cells lose polarity and turn into mesenchymal cells This is a process called epithelialmesenchymal transition (EMT). EMT has been found to be an essential biological process for epithelial-derived malignant cell invasion, migration, and anti-apoptosis [6]. During EMT, tumor cells can inhibit the transcription of epithelial genes (such as E-cadherin and keratin) and upregulate the transcription of mesenchymal genes (Vimentin and N-cadherin) to regulate multiple signals in the cancer microenvironment, so as to obtain the ability of migration and invasion. Transforming growth factor (TGF)-β signaling, which is upregulated in cancer development, usually triggers and drives the EMT process of cancer cells, and its role has been verified in a variety of human malignant tumors, including oral squamous cell carcinoma, hepatocellular carcinoma, pancreatic cancer, and esophageal cancer [7,8,9,10]. The purpose of this study is to explore the role and mechanism of MMP-9 in the EMT process of thyroid cancer (TC), so as to provide a basis for clinical exploration of invasion and metastasis process of TC, looking for biological markers of tumor metastasis and molecular intervention therapy
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