MMP-9 Knockdown Inhibits Oral Squamous Cell Carcinoma Lymph Node Metastasis in the Nude Mouse Tongue-Xenografted Model through the RhoC/Src Pathway

Autor: Ying Su, Feng Gao, Jinlin Wen, Xinyan Zhang, Suhong Chen, Panpan Yin, Yanlin Wu
Rok vydání: 2021
Předmět:
0301 basic medicine
Cancer Research
Article Subject
Axillary lymph nodes
Angiogenesis
RhoC
Mice
Nude
Pathology and Forensic Medicine
Metastasis
Mice
03 medical and health sciences
0302 clinical medicine
Nude mouse
medicine
Animals
Humans
Neoplasm Invasiveness
RC254-282
Mice
Inbred BALB C
Neovascularization
Pathologic
QH573-671
biology
Squamous Cell Carcinoma of Head and Neck
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Cell migration
Cell Biology
General Medicine
medicine.disease
biology.organism_classification
stomatognathic diseases
src-Family Kinases
030104 developmental biology
medicine.anatomical_structure
Matrix Metalloproteinase 9
rhoC GTP-Binding Protein
Gene Knockdown Techniques
Lymphatic Metastasis
030220 oncology & carcinogenesis
Cancer cell
biology.protein
Cancer research
Heterografts
Molecular Medicine
Mouth Neoplasms
Lymph
Cytology
Signal Transduction
Research Article
Zdroj: Analytical Cellular Pathology, Vol 2021 (2021)
Analytical Cellular Pathology (Amsterdam)
ISSN: 2210-7185
2210-7177
DOI: 10.1155/2021/6683391
Popis: 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.
Databáze: OpenAIRE
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