Values of MMP-2 and MMP-9 in Tumor Tissue of Basal-Like Breast Cancer Patients

Radenković, Sandra; Konjević, Gordana; Jurišić, Vladimir; Karadžić, Katarina; Nikitović, Marina; Gopčević, Kristina

doi:10.1007/s12013-013-9701-x

Cited by 42 publications

(34 citation statements)

References 28 publications

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“…Evidently, this sharply contrasts with the high levels of expression of MMP-9 found in the cytoplasm of both HER2-positive and triple-negative breast cancers cells. Hence, our findings support the conclusions of recently published studies indicating a positive correlation between high levels of MMP-9 expression and triple-negative breast cancers [20, 38, 39]. Our results may also explain the findings of La Rocca et al who showed that high serum levels of MMP-9 are present in HER2 amplified breast cancers [40].…”

Section: Discussionsupporting

confidence: 92%

MMP-9 expression varies according to molecular subtypes of breast cancer

et al. 2014

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BackgroundIn 2014, breast cancer remains a major cause of mortality worldwide mostly due to tumor relapse and metastasis. There is currently a great interest in identifying cancer biomarkers and signalling pathways mechanistically related to breast cancer progression. Matrix metalloproteinase-9 (MMP-9) is a member of matrix degrading enzymes involved in cancer development, invasion and metastasis. Our objective was to investigate MMP-9 expression in normal human breast tissue and to compare it to that of breast cancer of various histological grades and molecular subtypes. We also sought to correlate MMP-9 expression with the incidence of metastasis, survival rates and relapse in breast cancer patients.MethodsMMP-9 was first studied using in silico analysis on available DNA microarray and RNA sequencing data of human breast cancer tissues and human breast cancer cell lines. We next ascertained MMP-9 expression in both normal breast tissue and in human breast carcinoma tissue microarrays.ResultsSignificant increase in MMP-9 expression was found in breast cancer cells where compared to normal breast tissue. A positive correlation could also be established between elevated levels of MMP-9 and breast cancer of high histological grade. Furthermore, our results indicate that not only MMP-9 is differentially expressed between each molecular subset but also, more importantly MMP-9 overexpression revealed itself as a startling feature of triple-negative and HER2-positive breast cancers. Lastly, the clinical relevance of MMP-9 overexpression is strongly supported by its significant association with a higher incidence of metastasis and relapse.ConclusionsDifferential expression of MMP-9 reflects the extent of cellular differentiation in breast cancer cells and is closely related to the most aggressive subtypes of breast cancer. Hence, MMP-9 is a promising prognostic biomarker of high-grade breast cancer. In our opinion, MMP-9 expression could help segregate subsets of aggressive breast cancer into clinically meaningful subtypes.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-609) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

MMP-9 expression varies according to molecular subtypes of breast cancer

et al. 2014

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“…In patients with basal-like breast cancer, the activity of precursor and active forms of MMP-2 and MMP-9 was found to significantly increase with each advancing clinical stage of disease, and the activity of the precursor and active forms of MMP-9 in tumor tissue showed a positive association with tumor size. In addition, patients with lymph node involvement had higher activity of precursor and active forms of MMP-2 and the active form of MMP-9 than node-negative patients, and patients with steroid receptor-negative tumors had enhanced MMP-2 and MMP-9 activity compared with patients with luminal A tumors (16).…”

Section: Discussionmentioning

confidence: 93%

Doxorubicin induces drug resistance and expression of the novel CD44st via NF-κB in human breast cancer MCF-7 cells

et al. 2014

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Abstract. CD44, a major receptor for hyaluronan (HA), is a member of a class of adhesion molecules of unknown classification involved in cell proliferation, differentiation, migration, angiogenesis, and the presentation of specific cytokines to the corresponding receptors as well as in cell signaling transduction. It has recently been discovered that CD44, a marker of tumor stem cells, is involved in the drug resistance and invasion of multiple types of tumors. The 20 exons in the CD44 gene that are alternatively spliced, give rise to many CD44 isoforms, possibly including tumor-specific sequences. Dozens of CD44 isoforms have been found, to date, and the standard CD44 (CD44s) isoform is the most common. We recently showed that a novel short-tail isoform of CD44 (CD44st) was expressed in multidrug-resistant human breast cancer MCF-7/Adr cells. Moreover, the novel CD44st was able to interact with HA and regulate the expression of matrix metalloproteinase (MMP)-2 and MMP-9, which increased the invasive capability of MCF-7 cells through the Ras/MAPK signaling pathway. In the present study, we verified that MCF-7 cells subjected to drug pressure develop multidrug resistance to doxorubicin, and the expression levels of multidrug resistance protein 1 (MDR1), CD44st and nuclear factor-κB (NF-κB) mRNA and protein were gradually upregulated in a dose-dependent manner in MCF-7 cells treated with doxorubicin. HA increases the secretion of MMP-2 and MMP-9 in multidrug-resistant MCF-7 cells and affected the invasive ability of MCF-7 cells through the upregulation of CD44st expression, and such an effect was blocked by the NF-κB-specific inhibitor BMS-345541.

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“…However, ectopic or excess MMP-9 activity degrades various components of the extracellular matrix, especially type IV collagen of the basement membranes. 15 Not surprisingly, overexpression of MMP-9 is observed in many cancers and is the leading cause of tumor progression, promoting tumor invasion and metastasis. 16 MMP-9 also is involved in the pathogenesis of inflammatory disorders, such as arthritis.…”

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confidence: 99%