MMP-9 Knockdown Inhibits Oral Squamous Cell Carcinoma Lymph Node Metastasis in the Nude Mouse Tongue-Xenografted Model through the RhoC/Src Pathway
Oral squamous cell carcinoma (OSCC) is one of the most common types of cancers in developing countries. A major contributor to the high mortality rate of OSCC is the tendency of oral cancer cells to metastasize to lymph nodes around the head and neck during the early stages of cancer development. Ma...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Analytical Cellular Pathology |
| Online Access: | http://dx.doi.org/10.1155/2021/6683391 |
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| author | Panpan Yin Ying Su Suhong Chen Jinlin Wen Feng Gao Yanlin Wu Xinyan Zhang |
| author_facet | Panpan Yin Ying Su Suhong Chen Jinlin Wen Feng Gao Yanlin Wu Xinyan Zhang |
| author_sort | Panpan Yin |
| collection | DOAJ |
| description | Oral squamous cell carcinoma (OSCC) is one of the most common types of cancers in developing countries. A major contributor to the high mortality rate of OSCC is the tendency of oral cancer cells to metastasize to lymph nodes around the head and neck during the early stages of cancer development. Matrix metalloproteinase 9 (MMP-9), an endopeptidase, can degrade the extracellular matrix and basement membrane and plays a key role in tumor invasion and metastasis. In vitro, cell migration ability was conducted by scratching assays. We also investigated the interaction abilities between OSCC cells and vascular endothelial cells (ECs) by an adhesion assay and transendothelial migration assay. And we established a BALB/c nude mouse tongue-xenografted metastasis model to investigate the role of MMP-9 and explore its potential underlying mechanism in OSCC growth, lymph node metastasis, and angiogenesis in vivo. The results showed that knockdown of MMP-9 could significantly suppress OSCC cell migration, proliferation, interactions between endothelial cells, xenografted tumor growth, and angiogenesis and simultaneously markedly inhibited OSCC cell metastasis to mouse lymphonodi cervicales superficiales, axillary lymph nodes, and even distant inguinal lymph nodes. Mechanistic studies revealed that knockdown of MMP-9 also led to a decreased expression of RhoC, Src, and F-actin by RT-PCR, western blotting, and immunohistochemistry. And the bioinformatic analysis showed that MMP-9, RhoC, and Src mRNA expression was positively and linearly correlated in OSCC on TCGA database. Together, our findings indicated that MMP-9 plays a very important role in OSCC growth, migration, angiogenesis, and lymph node metastasis, and its potential mechanism may be mediated by RhoC and Src gene expression. |
| format | Article |
| id | doaj-art-7e8f6ec677c544d194e4d04a1723f9db |
| institution | Kabale University |
| issn | 2210-7177 2210-7185 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Analytical Cellular Pathology |
| spelling | doaj-art-7e8f6ec677c544d194e4d04a1723f9db2025-08-20T03:35:34ZengWileyAnalytical Cellular Pathology2210-71772210-71852021-01-01202110.1155/2021/66833916683391MMP-9 Knockdown Inhibits Oral Squamous Cell Carcinoma Lymph Node Metastasis in the Nude Mouse Tongue-Xenografted Model through the RhoC/Src PathwayPanpan Yin0Ying Su1Suhong Chen2Jinlin Wen3Feng Gao4Yanlin Wu5Xinyan Zhang6Beijing Institute of Dental Research, Beijing Stomatological Hospital & School of Stomatology, Capital Medical University, Beijing, ChinaBeijing Institute of Dental Research, Beijing Stomatological Hospital & School of Stomatology, Capital Medical University, Beijing, ChinaBeijing Institute of Dental Research, Beijing Stomatological Hospital & School of Stomatology, Capital Medical University, Beijing, ChinaBeijing Institute of Dental Research, Beijing Stomatological Hospital & School of Stomatology, Capital Medical University, Beijing, ChinaBeijing Institute of Dental Research, Beijing Stomatological Hospital & School of Stomatology, Capital Medical University, Beijing, ChinaBeijing Institute of Dental Research, Beijing Stomatological Hospital & School of Stomatology, Capital Medical University, Beijing, ChinaBeijing Institute of Dental Research, Beijing Stomatological Hospital & School of Stomatology, Capital Medical University, Beijing, ChinaOral squamous cell carcinoma (OSCC) is one of the most common types of cancers in developing countries. A major contributor to the high mortality rate of OSCC is the tendency of oral cancer cells to metastasize to lymph nodes around the head and neck during the early stages of cancer development. Matrix metalloproteinase 9 (MMP-9), an endopeptidase, can degrade the extracellular matrix and basement membrane and plays a key role in tumor invasion and metastasis. In vitro, cell migration ability was conducted by scratching assays. We also investigated the interaction abilities between OSCC cells and vascular endothelial cells (ECs) by an adhesion assay and transendothelial migration assay. And we established a BALB/c nude mouse tongue-xenografted metastasis model to investigate the role of MMP-9 and explore its potential underlying mechanism in OSCC growth, lymph node metastasis, and angiogenesis in vivo. The results showed that knockdown of MMP-9 could significantly suppress OSCC cell migration, proliferation, interactions between endothelial cells, xenografted tumor growth, and angiogenesis and simultaneously markedly inhibited OSCC cell metastasis to mouse lymphonodi cervicales superficiales, axillary lymph nodes, and even distant inguinal lymph nodes. Mechanistic studies revealed that knockdown of MMP-9 also led to a decreased expression of RhoC, Src, and F-actin by RT-PCR, western blotting, and immunohistochemistry. And the bioinformatic analysis showed that MMP-9, RhoC, and Src mRNA expression was positively and linearly correlated in OSCC on TCGA database. Together, our findings indicated that MMP-9 plays a very important role in OSCC growth, migration, angiogenesis, and lymph node metastasis, and its potential mechanism may be mediated by RhoC and Src gene expression.http://dx.doi.org/10.1155/2021/6683391 |
| spellingShingle | Panpan Yin Ying Su Suhong Chen Jinlin Wen Feng Gao Yanlin Wu Xinyan Zhang MMP-9 Knockdown Inhibits Oral Squamous Cell Carcinoma Lymph Node Metastasis in the Nude Mouse Tongue-Xenografted Model through the RhoC/Src Pathway Analytical Cellular Pathology |
| title | MMP-9 Knockdown Inhibits Oral Squamous Cell Carcinoma Lymph Node Metastasis in the Nude Mouse Tongue-Xenografted Model through the RhoC/Src Pathway |
| title_full | MMP-9 Knockdown Inhibits Oral Squamous Cell Carcinoma Lymph Node Metastasis in the Nude Mouse Tongue-Xenografted Model through the RhoC/Src Pathway |
| title_fullStr | MMP-9 Knockdown Inhibits Oral Squamous Cell Carcinoma Lymph Node Metastasis in the Nude Mouse Tongue-Xenografted Model through the RhoC/Src Pathway |
| title_full_unstemmed | MMP-9 Knockdown Inhibits Oral Squamous Cell Carcinoma Lymph Node Metastasis in the Nude Mouse Tongue-Xenografted Model through the RhoC/Src Pathway |
| title_short | MMP-9 Knockdown Inhibits Oral Squamous Cell Carcinoma Lymph Node Metastasis in the Nude Mouse Tongue-Xenografted Model through the RhoC/Src Pathway |
| title_sort | mmp 9 knockdown inhibits oral squamous cell carcinoma lymph node metastasis in the nude mouse tongue xenografted model through the rhoc src pathway |
| url | http://dx.doi.org/10.1155/2021/6683391 |
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