Plasma concentration and activity of matrix metalloproteinase 2 and 9 in patients with breast disease, breast cancer and at risk of developing breast cancer

Somiari, Stella; Shriver, Craig D.; Heckman, Caroline; Olsen, Cara; Hu, Hai; Jordan, Rick; Arciero, Cletus A.; Russell, Stephen J.; Garguilo, Gerald; Hooke, Jeffrey A.; Somiari, Richard I.

doi:10.1016/j.canlet.2005.03.003

Cited by 55 publications

(59 citation statements)

References 15 publications

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“…Furthermore, alternative methods to transcript analysis should be used in analyzing MMPs given the enzymatic nature of MMP. Indeed, previous studies have shown a raised level of MMP9 in the circulation of patients with cancer, including breast cancer using zymography (41,42). However, whether the effect on invasion by Ehm2 is MMP9 dependent and how FIGURE 7.…”

Section: Discussionmentioning

confidence: 98%

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

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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.

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Section: Discussionmentioning

confidence: 98%

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

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“…Several studies have been performed on the evaluation of plasma MMP concentrations in correlation with different diseases, including diabetes, atherosclerosis, inflammation and cancer. Of these studies, one was performed on breast cancer and revealed that the concentration of total MMP 2 and 9 was significantly higher in the plasma of patients with breast cancer compared with patients with benign breast diseases and the control groups (5). Another study performed on breast cancer demonstrated that the MMP 2 serum level was higher in patients positive for the estrogen receptor; furthermore, this study showed that a lower MMP 2 level was a predictor of disease-free and overall survival (6).…”

Section: Introductionmentioning

confidence: 99%

Plasma levels of matrix metalloproteinases 2 and 9 correlate with histological grade in breast cancer patients

et al. 2012

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Abstract. Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in the process of tumor invasion and metastasis that are found throughout tissues and also in the plasma. The aim of this study was to investigate whether the evaluation of plasma concentrations of MMPs 2, 3 and 9 may have clinical significance in breast cancer. Therefore, sera obtained from 80 patients with breast neoplasia (50 carcinomas and 30 fibroadenomas) were collected before and 96 h after surgery and the concentrations of MMPs 2, 3 and 9 were quantified using an enzyme-linked immunosorbent assay (ELISA). The mean expression level of MMP 2 was significantly higher in carcinoma compared with that in fibroadenoma patients, while there was no significant difference for MMPs 3 and 9. In addition, the group of carcinoma patients was analyzed in order to compare the mean values for each MMP obtained before and after surgery. However, the differences between pre-and post-surgery values for all three MMPs were not statistically significant. Furthermore, the plasma levels of each MMP were correlated with certain clinicopathological parameters of the tumors and we observed a significant and direct correlation between the concentrations of MMPs 2 and 9 and tumor histological grade. These data suggest that the quantification of plasma MMP 2 and MMP 9 levels may provide additional clinical information of the tumor and it is, therefore, a possible prognostic index for breast cancer.

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“…1 We read their article with concern, which described that total, active and activity of MMP were significantly increased in serum of cancer patients respect to benign diseases and control groups, concluding that serum MMP may classify patients with breast diseases. Surprisingly, the authors have just published an almost overlapping study using plasma samples following the same research protocol, 2 reporting that also plasma MMP concentration and activity may permit subclassification of patients with breast disorders.…”

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confidence: 99%

“…2,18,19 The faithful determination of MMP-2 and -9 circulating in blood depends on the procedure of blood sampling/handling, a methodological issue discussed extensively in this Journal 20 and analytical journals. [11][12][13][14][15][16][17] Although these articles unequivocally demonstrated the ''artificially'' higher levels of serum MMPs with respect to plasma, manuscripts ignore these statements and continue to publish based on the measurements of serum MMPs.…”

mentioning

confidence: 99%

“…(reporting as ''still unresolved'' the preanalytical issue of blood sampling) are in strong contrast with a wide number of publications that extensively demonstrated (not only in analytic journals [11][12][13][14][15][16][17] but also in this 18,20 and other cancer journals 2,19 ) the presence of MMP-9 forms in higher amounts in serum, not only related to the disease but mainly linked to coagulation/fibrinolytic pathways. In fact, the use of anticoagulants limits the release and activation of MMP-9 forms from blood cells.…”

mentioning

confidence: 99%

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Gelatinase concentrations and zymographic profiles in human breast cancer: Matrix metalloproteinases circulating in plasma are better markers for the subclassification and early prediction of cancer: The coagulation/fibrinolysis pathways alter the release, activation and recovery of different gelatinases in serum

Mannello

Tonti

2007

Intl Journal of Cancer

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Plasma concentration and activity of matrix metalloproteinase 2 and 9 in patients with breast disease, breast cancer and at risk of developing breast cancer

Cited by 55 publications

References 15 publications

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

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

Plasma levels of matrix metalloproteinases 2 and 9 correlate with histological grade in breast cancer patients

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