Targeting Matrilysin and Its Impact on Tumor Growth <i>In vivo</i>: The Potential Implications in Breast Cancer Therapy

Jiang, Wen Guo; Davies, Gaynor; Martin, Tracey Amanda; Parr, Christian; Watkins, Gareth; Mason, Malcolm David; Mokbel, Kefah; Mansel, Robert Edward

doi:10.1158/1078-0432.ccr-05-0275

Cited by 93 publications

(87 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Matrix metalloproteinase -7 (matrilysin 1) is a stromelysin, that degrades type IV collagen, fibronectin and laminin. It was shown that MMP-7 is aberrantly expressed in human breast tumours and that elimination of MMP-7 is associated with low invasiveness and slow tumour growth (Jian et al, 2005). Likewise, it has been recently reported that MMP-7 overexpression in breast cancer (MCF-7) cells enhances cellular invasiveness and activation of proMMP-2 and MMP-9 (Wang et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Study of matrix metalloproteinases and their inhibitors in breast cancer

et al. 2007

View full text Add to dashboard Cite

An immunohistochemical study was performed using tissue microarrays and specific antibodies against matrix metalloproteinases (MMPs) 1, 2, 7, 9, 11, 13, 14, and their tisullar inhibitors (TIMPs) 1, 2, and 3. More than 2600 determinations on cancer specimens from 131 patients with primary ductal invasive tumours of the breast (65 with and 66 without distant metastasis) and controls were performed. Staining results were categorised using a score based on the intensity of the staining and a specific software program calculated the percentage of immunostained cells automatically. We observed a broad variation of the total immunostaining scores and the cell type expressing each protein. There were multiple and significant associations between the expression of the different MMPs and TIMPs evaluated and some parameters indicative of tumour aggressiveness, such as large tumour size, advanced tumour grade, high Nottinham prognostic index, negative oestrogen receptor status, peritumoural inflammation, desmoplastic reaction, and infiltrating tumoural edge. Likewise, the detection of elevated immunohistochemical scores for MMP-9, 11, TIMP-1, and TIMP-2, was significantly associated with a higher rate of distant metastases. The expression of MMP-9 or TIMP-2 by tumour cells, MMP-1, 7, 9, 11, 13, or TIMP-3 by fibroblastic cells, and MMP-7, 9, 11, 13, 14, TIMP-1, or TIMP-2 by mononuclear inflammatory cells, was also significantly associated with a higher rate of distant metastases.

show abstract

Section: Discussionmentioning

confidence: 99%

Study of matrix metalloproteinases and their inhibitors in breast cancer

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Other methods to inhibit or deactivate MT1-MMP have been reported. For example, Ro-28-2653, an inhibitor with high selectivity for MMP2, MMP9, and MT1-MMP has been shown to inhibit the in vitro invasion and reduce the growth of breast tumours of breast cancer cells (19 (25). It is indicated therefore that an approach targeting multiple MMPs may be necessary to have an impact when considering cancer therapies.…”

Section: Discussionmentioning

confidence: 99%

“…Plasmid, extracted and purified using a plasmid extraction kit (Qiafilter, Qiagen, Crawley, UK), was introduced to a retroviral packaging cell line, PT67, using electroporation as previously described (25), followed by selection with G418 containing-medium for over 3 weeks. Viral titres from stably transfected PT67 cells were tested using NIH3T3 cells, and were found to be on average 8x10 5 cfu/ml.…”

Section: Construction Of Retroviral Hammerhead Ribozyme Transgenes Tamentioning

confidence: 99%

Expression of membrane type-1 matrix metalloproteinase, MT1-MMP in human breast cancer and its impact on invasiveness of breast cancer cells

Jiang¹,

Davies²,

Martin³

et al. 2006

Int J Mol Med

Self Cite

115

View full text Add to dashboard Cite

Abstract. MT1-MMP (membrane type-1 matrix metalloproteinase), otherwise known as MMP14 is a proteolytic enzyme known to be involved in degradating extracellular matrix and assist progression of cancer invasion and progression. We investigated the impact of targeting the expression of MT1-MMP in breast cancer and its clinical relevance. Human breast cancer cell line MDA-MB-231 was used. Expression of MT1-MMP in the breast cancer cell line was manipulated by way of retroviral ribozyme transgene. The in vitro invasion, growth and cell migration were determined on cell lines transfected with either the transgene or control plasmid. Protein and message levels of MMP14 was also assessed using immunohistochemistry and real-time quantitative analysis, and correlated with clinical and pathological information of the patients. Retroviral ribozyme transgene to human MT1-MMP successfully knocked down the levels of MT1-MMP mRNA from MDA-MB-231 cells. Reduction of MT1-MMP from the breast cancer cells resulted in significant reduction of in vitro invasiveness and loss of response to an invasion stimulus, HGF, compared with control and wild-type cells. The invasion index for MT1-MMP knockdown cells were 13±3

show abstract

“…A standard procedure was used as previously described (18,19). Cells were plated into a 96-well plate (2,500 cells per well).…”

Section: In Vitro Cell Growth Assaymentioning

confidence: 99%

Clinical Implications of the Influence of Ehm2 on the Aggressiveness of Breast Cancer Cells through Regulation of Matrix Metalloproteinase-9 Expression

Ye²,

Mansel³

et al. 2010

Molecular Cancer Research

Self Cite

View full text Add to dashboard Cite

Ehm2, a member of NF2/ERM/4.1 superfamily, has been indicated in disease progression and metastasis of prostate cancer. However, its function and implication in malignancies remain largely unknown. The present study aimed to examine the role of Ehm2 in breast cancer. We first constructed a hammerhead ribozyme transgene to knock down Ehm2 expression in breast cancer cells. The effect on growth, cell matrix adhesion, motility, and invasion following knockdown of Ehm2 was then investigated using in vitro models. Reduction of Ehm2 had inhibitory effects on in vitro growth and invasion of breast cancer cells. Flow cytometric analysis showed that knockdown of Ehm2 induced apoptosis. Knockdown of Ehm2 also significantly decreased matrix metalloproteinase 9 mRNA and protein levels, as well as the corresponding enzymatic activity, and consequently led to a reduction of the invasion. The expression pattern of Ehm2 in a cohort of breast specimens (normal, n = 33; cancer, n = 127) was analyzed using both quantitative real-time PCR and immunohistochemical staining. Increased expression of Ehm2 in breast cancer was seen at both mRNA and protein levels. Higher levels of Ehm2 transcripts were correlated with disease progression, metastasis, and poor prognosis. Disease-free survival of the patients with lower levels of Ehm2 was 135.8 (95% confidence interval, 125.1-146.5) months, significantly longer compared with 102.5 (95% confidence interval, 78.7-126.4) months of patients with higher levels of Ehm2 expression (P = 0.039). Taken together, increased Ehm2 expression correlates with poor prognosis and metastasis. Ehm2 may promote the invasive ability of breast cancer cells via regulation of matrix metalloproteinase 9. Mol Cancer Res; 8(11); 1501-12.

show abstract

Targeting Matrilysin and Its Impact on Tumor Growth In vivo: The Potential Implications in Breast Cancer Therapy

Cited by 93 publications

References 27 publications

Study of matrix metalloproteinases and their inhibitors in breast cancer

Study of matrix metalloproteinases and their inhibitors in breast cancer

Expression of membrane type-1 matrix metalloproteinase, MT1-MMP in human breast cancer and its impact on invasiveness of breast cancer cells

Clinical Implications of the Influence of Ehm2 on the Aggressiveness of Breast Cancer Cells through Regulation of Matrix Metalloproteinase-9 Expression

Contact Info

Product

Resources

About