Matrix metalloproteinase-2 as a target for head and neck cancer therapy

Chien, Ming Hsien; Lin, Chiao‐Wen; Cheng, Chao; Wen, Yu‐Ching; Yang, Shun Fa

doi:10.1517/14728222.2013.740012

Cited by 82 publications

(90 citation statements)

References 110 publications

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“…MMP-2, which is a zinc-dependent proteinase, is associated with the progression, invasion and metastasis of squamous cell carcinoma, and is a potential prognostic indicator of this type of cancer (30,31). In the present study, rAd/p53 treatment exhibited a strong inhibitory effect on MMP-2 expression levels and the expression of these two genes demonstrated a negative correlation.…”

Section: A B C Dsupporting

confidence: 51%

Antitumor effects of recombinant human adenovirus-p53 against human cutaneous squamous cell carcinoma in mice

Wang

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. The present study was conducted to identify the anti-tumor effects of rAd/p53, which is a recombinant human serotype 5 adenovirus, in cutaneous squamous cell carcinoma (cSCC). Mouse models of human cSCC were constructed by injecting human cutaneous squamous cell carcinoma cells into both flanks of nude mice. Subsequently, the 75 nude mice with cSCC xenograft tumors were randomly divided into recombinant human serotype 5 adenovirus (rAd)/p53, rAd/p53 + 5-fluorouracil (5-Fu) and 5-Fu groups. One side of the tumors was administered the therapeutic agents as the therapeutic group, whereas the remaining side was treated with medical saline as the control. At 24, 48, 72, 120 and 168 h post-intratumoral injection, alterations in tumor volume, tumor necrosis and the expression of several tumor-associated genes, including Smad4, Brca1 and matrix metalloproteinase (MMP-2), were analyzed. Compared with its control group, the rAd/P53 group exhibited a significantly increased tumor necrosis ratio. In addition, Smad4 and Brca1 expression levels increased significantly at various time points (P<0.05), and MMP-2 expression decreased significantly (P<0.05). In the rAd/p53 + 5-Fu group, the tumor necrosis ratio, and Smad4 and Brca1 expression levels also significantly increased at various time points (P<0.05). MMP-2 gene transcription gradually decreased, high expression of Smad4 was prolonged, and high expression of Brca1 was observed in the early period following treatment compared with the rAd/P53 group. In addition, p53 expression exhibited a positive correlation with the tumor necrosis ratio and Smad4 expression, and showed a negative correlation with MMP-2 gene transcription (P<0.05). These findings indicate that rAd/p53 has a potent anti-tumor effect in cSCC via the promotion of tumor necrosis and regulating the expression of various tumor-associated genes.

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Section: A B C Dsupporting

confidence: 51%

Antitumor effects of recombinant human adenovirus-p53 against human cutaneous squamous cell carcinoma in mice

Wang

et al. 2016

Experimental and Therapeutic Medicine

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“…Among these proteases, MMP-2 has been reported to be significantly correlated with the invasion and metastasis of human cancers, as evidenced by many studies which showed that inhibiting the expression of MMP-2 can suppress the invasion and metastasis of cancer cells (Bjorklund et al, 2005;Masson et al, 2006;Yang et al, 2013aYang et al, , 2015. For head and neck cancers, an inhibition of MMP-2 activity or synthesis also reportedly results in the suppression of metastasis of these tumors (Rosenthal et al, 2006;Chien et al, 2013). With regards to the pathogenesis of NPC, its association with MMP-2 is supported by a molecular epidemiological study which showed that the MMP-2 -1306C/T promoter polymorphism was associated with an increased risk of NPC, and enzyme linked immunosorbant assay studies which have shown that a high level of MMP-2 is associated with poor survival and high incidence of lymph node metastasis in these patients (Wong et al, 2004;Shao et al, 2011;Huang et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Most MMPs have been implicated in the tumorigenesis of various human malignancies (Chien et al, 2013;Yang et al, 2016). Among these proteases, MMP-2 has been reported to be significantly correlated with the invasion and metastasis of human cancers, as evidenced by many studies which showed that inhibiting the expression of MMP-2 can suppress the invasion and metastasis of cancer cells (Bjorklund et al, 2005;Masson et al, 2006;Yang et al, 2013aYang et al, , 2015.…”

Section: Discussionmentioning

confidence: 99%

“…MMPs are a family of zinc-dependent endopeptidases that are collectively capable of degrading most components of the basement membrane and ECM, and increased expressions of these enzymes are detected in almost all human cancers and have been associated with the aggressiveness of various neoplasms (Cox et al, 2001;Shuman Moss et al, 2012). Among the 25 already identified MMP members, MMP-2 and MMP-9 are type IV collagen proteins involved in the degradation of basement membrane structures and thus play an important role in the process of cancer cell invasion and metastasis (Nelson et al, 2000;Chien et al, 2013;Yang et al, 2016). Unlike other MMPs which are closely regulated at the level of transcription, MMP-2 is often constitutively expressed and controlled through a unique mechanism of enzyme activation involving extracellular hydrolysis of cysteine-Zn bonds (Sternlicht et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Rubus idaeusInhibits Migration and Invasion of Human Nasopharyngeal Carcinoma Cells by Suppression of MMP-2 through Modulation of the ERK1/2 Pathway

et al. 2017

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Nasopharyngeal carcinoma (NPC) is characterized by a high incidence of metastasis in the neck lymph nodes, resulting in a poor prognosis and posing challenges for treatment. In this study, we investigated the in vitro antimetastatic properties of Rubus idaeus extract (RIE) on human nasopharyngeal carcinoma cells. HONE-1, NPC-39 and NPC-BM cells were subjected to RIE treatment, and effects on the migration and invasion of tumor cells were analyzed. The results showed that RIE suppressed the migration and invasion of NPC cells. Gelatin zymography assay, Western blotting and real-time PCR showed that matrix metalloproteinases-2 (MMP-2) enzyme activity, protein expression and mRNA levels were down-regulated by RIE treatment. To identify the signaling pathway, mitogen-activated protein kinase proteins were examined, which showed that phosphorylation of ERK1/2 was inhibited after the treatment of RIE. In summary, our data showed that RIE inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 by The American Journal of Chinese Medicine, Vol. 45, No. 7, 1557-1572© 2017 down-regulating the ERK1/2 signaling pathway, suggesting that Rubus idaeus may serve as chemotherapeutic and chemopreventive agent for NPC.

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“…The development of OSCC is a multistep process requiring the accumulation of multiple genetic alterations, affected by a patient's genetic predisposition and by environmental influences, including alcohol and tobacco consumption, betel-quid chewing, chronic inflammation, and viral infection [1][2][3][4][5][6]. Expression of a gene may be affected by a single-nucleotide polymorphism (SNP) located within the promoter or other regulatory regions of the gene, and the production or activity of its translated protein is further modulated.…”

Section: Introductionmentioning

confidence: 99%

Impact of VEGF‐C Gene Polymorphisms and Environmental Factors on Oral Cancer Susceptibility in Taiwan

Chen¹

2013

Otolaryngol.--head neck surg.

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Background: Oral cancer, which is the fourth most common male cancer, is associated with environmental carcinogens in Taiwan. Vascular endothelial growth factor (VEGF)-C, an angiogenic/lymphangiogenic factor with high expression levels in tumor tissues, plays important roles in the development of several malignancies. This study was designed to examine associations of five VEGF-C gene polymorphisms with the susceptibility to and clinicopathological characteristics of oral squamous cell carcinoma.

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Matrix metalloproteinase-2 as a target for head and neck cancer therapy

Cited by 82 publications

References 110 publications

Antitumor effects of recombinant human adenovirus-p53 against human cutaneous squamous cell carcinoma in mice

Antitumor effects of recombinant human adenovirus-p53 against human cutaneous squamous cell carcinoma in mice

Rubus idaeusInhibits Migration and Invasion of Human Nasopharyngeal Carcinoma Cells by Suppression of MMP-2 through Modulation of the ERK1/2 Pathway

Impact of VEGF‐C Gene Polymorphisms and Environmental Factors on Oral Cancer Susceptibility in Taiwan

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