Expression of matrix metalloproteinase 1, matrix metalloproteinase 2, and matrix metalloproteinase 9 in carcinoma of the head and neck (original) (raw)
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Cureus
Background: One of the most prevalent malignancies in India is oral squamous cell carcinoma (OSCC), which is found in more than 90% of cancer cases and has a reduced survival rate of 30%. Matrix metalloproteinases (MMPs) are zinc-containing and calcium-dependent endopeptidases that regulate angiogenesis, migration, and proliferation. MMP-9 in OSCC increases tumor progression through angiogenesis, degrades the basement membrane, and facilitates metastasis by changes in tissue shape. Its overexpression in OSCC has also been shown to have prognostic significance. Aim: This study aims to evaluate the serum levels of MMP-9 in OSCC patients and healthy controls and to correlate with its clinicopathological staging. Materials and methods: This study included 40 individuals; 20 patients with OSCC and 20 healthy controls. MMP-9 was determined in serum samples utilizing enzyme-linked immunosorbent assays. Results: Descriptive statistics showed that 90% of the patients included in the OSCC groups were above 40 years, and 85% were males. There was a significant increase in the serum level of MMP-9 in OSCC patients compared to healthy controls with a mean difference of +28% (393.21 pg/ml) and a significant p-value of 0.001. (1365.80 ±236.414 pg/ml vs 973.67 ± 83.416 pg/ml). There was a significant increase in the serum levels of MMP-9 among the tumor stages and nodal involvement with a significant p-value of 0.002 and 0.001. No significant association was found between the age and gender groups in OSCC patients and serum levels of MMP-9. Conclusion: MMP-9 was significantly increased in OSCC when compared to healthy controls. Hence, MMP-9 can be used as a prognostic indicator in assessing tumor staging and nodal involvement.
Translational Cancer Research, 2018
Background: Biomarkers like programmed death ligand-1 (PDL1) have become a focal point for immunotherapeutic checkpoint inhibition in head and neck squamous cell carcinoma (HNSCC). However, it's only part of the total immunosuppressive biomarker profile of HNSCC cells. Matrix metalloproteinases (MMPs) are enzymes that break down the basement membrane allowing cancer cells to metastasize and play an important role in the tumor microenvironment. MMPs can also activate certain cytokines, growth factors, and chemokines post-translationally. The objective of this study was to determine MMP and biomarker profiles of seven different HNSCC cell lines. Methods: Authenticated cell lines were grown in minimal media at 1×10 6 viable cells/mL and incubated at 37 ℃. After 24 hrs supernatants were collected, and adhering cells were lysed. Multiplex immunoassays were used to determine MMP1, MMP7, MMP9, IL-6, VEGFA, IL-1α, TNF-α, GM-CSF, IL-1RA, and IL-8 concentrations in supernatants. ELISAs were used to determine PDL1, CD47, FASL, and IDO concentrations in cell lysates. A one-way ANOVA was fit to examine log-transformed concentrations of biomarkers between seven HNSCC cell lines, and pairwise group comparisons were conducted using posthoc Tukey's honest significance test (α=0.05). Results: Significant differences (P<0.05) in MMP and biomarker concentrations were found between the seven HNSCC cell lines. For example, MMP9 was highest in SCC25 and UM-SCC99, MMP7 was highest in SCC25 and UM-SCC19, and MMP1 was highest in SCC25. Conclusions: These results suggest different patients' HNSCC cells can express distinct profiles of select biomarkers and MMPs, which could be due to metastatic stage of the cancer, primary tumor site, type of tissue the tumor originated from, or genomic differences between patients. MMP and biomarker expression profiles should be considered when choosing cell lines for future studies. The results support the reason for personalized medicine and the need to further investigate how it can be used to treat HNSCC.
MMP-7, MMP-8, and MMP-9 in oral and cutaneous squamous cell carcinomas
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 2015
Objectives. Oral squamous cell carcinoma (OSCC) and cutaneous squamous cell carcinoma (CSCC) are epithelial neoplasms, of which OSCC has a worse prognosis. Matrix metalloproteinases (MMPs) are involved in the initiation, invasion, metastasis, and defense of cancer. This study aimed to compare differences in MMP expression in these cancers. Study Design. Sixty-one patients with early-stage (T1-T2 N0 M0) cancers, of which 36 were OSCC and 25 CSCC, were enrolled into this study. Immunohistochemical staining was performed with MMP-7, MMP-8, and MMP-9 antibodies. Results. MMP-7 expression was stronger in OSCC than in CSCC, mainly in the invasive front. MMP-8 was absent and MMP-9 was mildly expressed in OSCC and CSCC cells. However, MMP-8 and MMP-9 were positive in peritumoral inflammatory cells in both cancers. In addition, MMP-7, MMP-8, and MMP-9 were not associated with the overall survival of patients with OSCC and CSCC patients. Conclusions. The increased expression of MMP-7 in the invasive front may partly explain the aggressiveness of OSCC.
Anticancer research, 2014
Head and neck squamous cell cancer (HNSCC) includes tumors of various anatomical sites sharing common etiological factors. Serum levels of MMP1, MMP2, and MMP9 were analyzed in patients with oropharyngeal, laryngeal, and hypopharyngeal carcinomas in an effort to elucidate the pathobiology and in order to find useful biomarkers of site-specific HNSCC. The study group comprised of 46 patients with HNSCC (21 with oropharyngeal, 21 with laryngeal and 4 with hypopharyngeal cancer). Serum levels of MMP1, -2, and -9 were determined by the MAGPIX multiplex method. P16 protein was detected by immunohistochemistry. Serum levels of matrix metalloproteinases (MMPs) were correlated with clinicopathological features of carcinomas and were compared with respect to tumor site. Significant correlations were confirmed between p16 positivity and oropharyngeal cancer, MMP1 and p16 positivity, and recurrence and smoking. Statistically significant differences in serum levels of MMPs between cancer of dif...
International Journal of Cancer, 2003
Expression of 12 matrix metalloproteinases (MMPs) after exposure of human melanoma cell lines C32TG and Mewo to nitric oxide (NO) was investigated by the reverse transcription-polymerase chain reaction. Expression of the mRNA of MMP-1, -3, -10 and -13 in C32TG cells was transcriptionally enhanced in a dose-dependent manner by exposure to an NO donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP) and mRNA expression of MMP-1 and -10 was similarly enhanced in Mewo cells. Exposure of C32TG cells to NO increased the MMP-1 protein concentration in the culture medium. Testing with the luciferase gene fused to the 1.5 Kbp 5-flanking region of the human MMP-1 gene showed that exposure to NO upregulated MMP-1 promoter activity in C32TG cells.
Low plasma levels of matrix metalloproteinase 9 permit increased tumor angiogenesis
Oncogene, 2002
Angiogenesis is essential for tumor growth and blocking this process might be a valid tool for the control of cancer growth. We showed previously that tumor angiogenesis in integrin a1-null mice is reduced compared to that of wild type animals and that over-expression of matrix metalloproteinase 9 (MMP-9) in the a1-null and consequent generation of angiostatin (an inhibitor of endothelial cell growth) from circulating plasminogen was implicated in the mechanism of tumor inhibition. Our ®ndings suggested that secretion of excess MMPs generates inhibitors of endothelial cell proliferation, including but not necessarily limited to angiostatin, resulting ultimately in auto-inhibition of angiogenesis. Thus MMP inhibitors used as anti-tumor drugs might in fact cause a paradoxical increase in tumor angiogenesis and tumor growth. In order to determine whether MMP-9 expression was directly involved in the regulation of tumor growth, we speci®cally inhibited or enhanced MMP-9 synthesis in vitro and in vivo, and subsequently analysed primary endothelial cell proliferation and angiostatin synthesis, as well as tumor vascularization and development. We provide evidence that reduction of plasma levels of MMP-9 in either normal or integrin a1null mice leads to decreased synthesis of angiostatin and consequent increased tumor growth and vascularization. In contrast, speci®cally enhancing MMP-9 expression in vivo caused a reduction in tumor vascularization. These ®ndings are the opposite to other studies suggesting a pro-tumorigenic role for MMP-9, and may account for some of the recently observed failures of anti MMP therapy in tumor treatment.
Matrix metalloproteinase-7, -8, -9, -15, and -25 in minor salivary gland adenoid cystic carcinoma
Pathology - Research and Practice, 2021
Knowledge on the role of matrix metalloproteinases (MMPs) in adenoid cystic carcinoma (ACC) is limited. MMPs are capable of degrading almost all extracellular and pericellular components to promote invasion and metastasis. This study aimed to evaluate the immunohistochemical expression of MMP-7,-8,-9,-15, and-25 in ACC and to relate the results with clinicopathological factors and survival. The study included 68 patients with minor salivary gland ACC treated at the Helsinki University Hospital (Helsinki, Finland) in 1974 to 2012. Samples from 52 patients were available, consisting of 44 primary tumours and eight recurrent tumours. We scored immunostaining of MMP-7,-8,-9,-15, and-25 and analysed the immunoscore against clinical and pathological parameters using statistical correlation test. MMP-9 immunoexpression in pseudocysts of ACC and in peritumoural inflammatory cells associated with better survival and fewer treatment failures. High tumoural MMP-7 and-25 associated with better survival. High tumoural MMP-15 associated with poorer survival and high tumoural MMP-9 with advanced stage and regional recurrences. Tumour cells did not show MMP-8 immunopositivity. These results suggest that MMP-9 may contribute to ACC carcinogenesis in different roles. MMP-7,-8, and-9 can stimulate signalling pathways that may promote tissue modulation and metastatic potential. MMP-15 and-25 may reflect prognosis.
Immunoexpression of MMP-9 in Metastasis of Oral Squamous Cell Carcinoma
2019
Ab s t r Ac t Introduction: Oral squamous cell carcinoma (OSCC) is the most common malignancy of the head and the neck. The unfavorable prognosis of OSCC is mainly due to extensive local invasion and frequent spread to the lymph node. Studies have supported that the metastatic potential of carcinoma might correlate with the degree of enzymatic degradation of basement membrane type IV collagen. MMP-9 a family member of zinc-dependent endopeptidases causes degradation of type IV collagen and plays a relevant role in tumor invasion and metastasis. Aim and objective: To evaluate the role of MMP-9 in the invasion and metastasis of OSCC and to examine whether high levels of MMP-9 expression have any prognostic potential. Materials and methods: MMP-9 expression was examined using the immunohistochemistry procedure in 30 OSCC cases with and without lymph node metastasis and in 10 normal controls. One set from each case and control was stained with the hematoxylin and eosin stain. The expres...
Matrix metalloproteinase-2 (MMP-2) and MMP-9 expression in invasive ductal carcinoma of the breast
Pathology - Research and Practice, 2011
Breast Invasive ductal carcinoma Matrix matalloproteinase-2 Matrix metalloproteinase-9 Triple-negative breast carcinoma a b s t r a c t Matrix metalloproteinase-2 (MMP-2) and MMP-9 are gelatinases that play a role in the invasion and metastasis of cancer through the destruction of the basal membrane and extracellular matrix. In this study, we investigated the immunohistochemical expression of MMP-2 and MMP-9 and the correlation between the expression levels and prognostic clinicopathological parameters in 140 patients with invasive ductal carcinoma (IDC). The staining scores for MMP-9 were negative in 21 cases (15%), mild in 27 cases (19%), and strong in 92 cases (66%). MMP-9 expression was increased in high-grade (p = 0.001), triple-negative (ER, PR, HER2 negative) (p = 0.006), and ER-negative tumors (p = 0.004) and tumors with distant metastases (p = 0.028). MMP-9 expression was increased in cases with HER2 overexpression/amplification, but no statistically significant difference was found (p = 0.215). No correlation was found between lymph node metastasis or tumor size and MMP-9 expression (p = 0.492 and p = 0.448, respectively). The staining scores for MMP-2 in 140 cases were negative in 10 cases (7%), mild in 25 cases (18%), and strong in 105 cases (75%). MMP-2 expression was increased in ER-negative and high-grade tumors in the lymph node-negative group (p = 0.025 and 0.026, respectively). High MMP-9 expression was associated with a shorter disease-free survival and overall survival times (p = 0.042 and p = 0.046, respectively). In conclusion, increased MMP-9 expression is related to poor prognostic clinicopathological factors in IDC, and hence, it can be utilized as a supplementary prognostic marker. The role of MMP-2 expression in the prognosis of IDC is rather limited.