Expression of matrix metalloproteinases (MMP-2 and -9) and their inhibitors (TIMP-1 and -2) in prostate cancer tissue

Brehmer, Bernhard; Biesterfeld, Stefan; Jakse, G.

doi:10.1038/sj.pcan.4500657

Cited by 92 publications

(90 citation statements)

References 32 publications

(25 reference statements)

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“…Our results are similar to those published by Lichtinghagen et al (2002) (14), who showed MMP-2 underexpression in prostate cancer tissue using RT-PCR. Conversely, they observed higher expression of MMP-2 at the protein level using immunohistochemistry, a result later confirmed by Brehmer et al (15), indicating that there is a discrepancy between the levels of MMP-2 mRNA and protein in prostate cancer.…”

Section: Discussionsupporting

confidence: 55%

Underexpression of MMP-2 and its regulators, TIMP2, MT1-MMP and IL-8, is associated with prostate cancer

et al. 2012

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Prostate cancer (PCa) is a common disease with a multifactorial and complex etiology. It is the most common malignancy in the male and the second leading cause of death in many countries, including Brazil. Estimates for 2011 indicate that 903,500 new cases and 258,400 deaths relatVol. 38 (2): 167-174; March -April, 2012 Objective: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their regulators. The purpose of this study was to investigate whether MMP-2 and its specifi c regulators, TIMP-2, MT1-MMP and IL-8, are expressed in a reproducible, specifi c pattern and if the profi les are related to prognosis and clinical outcome of prostate cancer (PCa). Materials and Methods: MMP-2, TIMP-2, MT1-MMP and IL-8 expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in freshly frozen malignant and benign tissue specimens collected from 79 patients with clinically localized PCa who underwent radical prostatectomies. The control group consisted of 11 patients with benign prostate hyperplasia (BPH). The expression profi le of the MMP-2 and its regulators were compared using Gleason scores, pathological stage, pre-operative PSA levels and the fi nal outcome of the PCa. Results: The analysis of 79 specimens of PCa revealed that MMP-2, TIMP-2, MT1-MMP and IL-8 were underexpressed at 60.0%, 72.2%, 62.0% and 65.8%, respectively, in malignant prostatic tissue in relation to BPH samples. Considering the prognostic parameters, we demonstrated that high Gleason score tumors (≥ 7) overexpressed MMP-2 (p = 0.048) and TIMP-2 (p = 0.021), compared to low Gleason score tumors (< 7). Conclusion: We have demonstrated that MMP-2 and its regulators are underexpressed in PCa. Alternatively, overexpression of MMP-2 and TIMP-2 was related to higher Gleason score tumors. We postulate that alterations in metalloproteinase expression may be important in the control of tissue homeostasis related to prostate carcinogenesis and tumor behavior. Underexpression of MMP-2 and its

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Section: Discussionsupporting

confidence: 55%

Underexpression of MMP-2 and its regulators, TIMP2, MT1-MMP and IL-8, is associated with prostate cancer

et al. 2012

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“…TIMP-1, -2, and -3 mRNA molecules and proteins were detected in human prostate cancer specimens [22,23], and TIMP-1 has been shown in various studies to be downregulated in prostate cancer as compared to normal prostate [22,24]. A study of TIMP-1, -2, and -3 mRNA showed significant reduction of TIMP 2 and 3 in prostate cancer, as well as significant increases in the ratios of MMP-9 to TIMP-1, -2, and -3, and in the ratio of MMP-14 to TIMP-3 [23].…”

Section: Introductionmentioning

confidence: 97%

Coordinated peak expression of MMP-26 and TIMP-4 in preinvasive human prostate tumor

et al. 2006

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The identification of novel biomarkers for early prostate cancer diagnosis is highly important because early detection and treatment are critical for the medical management of patients. Disruption in the continuity of both the basal cell layer and basement membrane is essential for the progression of high-grade prostatic intraepithelial neoplasia (HGPIN) to invasive adenocarcinoma in human prostate. The molecules involved in the conversion to an invasive phenotype are the subject of intense scrutiny. We have previously reported that matrix metalloproteinase-26 (MMP-26) promotes the invasion of human prostate cancer cells via the cleavage of basement membrane proteins and by activating the zymogen form of MMP-9. Furthermore, we have found that tissue inhibitor of metalloproteinases-4 (TIMP-4) is the most potent endogenous inhibitor of MMP-26. Here we demonstrate higher (p<0.0001) MMP-26 and TIMP-4 expression in HGPIN and cancer, compared to non-neoplastic acini. Their expression levels are highest in HGPIN, but decline in invasive cancer (p<0.001 for each) in the same tissues. Immunohistochemical staining of serial prostate cancer tissue sections suggests colocalization of MMP-26 and TIMP-4. The present study indicates that MMP-26 and TIMP-4 may play an integral role during the conversion of HGPIN to invasive cancer and may also serve as markers for early prostate cancer diagnosis.

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“…The MMPs ' activities are subject to regulation by tissue inhibitors of metalloproteases (TIMPs) [ 55 ] . An association between MMPs and/or TIMPs expression and parameters indicative of prostate cancer aggressiveness has also been reported.…”

Section: Mmpsmentioning

confidence: 99%

Angiogenesis in prostate cancer: onset, progression and imaging

et al. 2012

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What's known on the subject? and What does the study add?Today, angiogenesis is known to play a key role in cancer growth and development. Emerging cancer treatments are based on the suppression of angiogenesis, and modern imaging techniques investigate changes in the microvasculature that are caused by angiogenesis. As for other forms of cancers, angiogenesis is well recognised as a fundamental process in the development of prostate cancer.The novelty of this extensive report on angiogenesis in cancer, with particular attention on prostate cancer and the imaging techniques able to detect it, is the new prospective to the subject. In contrast with the other available reviews, this report goes from ‘theory’ to ‘practice’, establishing a clear link between angiogenesis development and imaged angiogenesis features. Once the key role of angiogenesis in the development of cancer and in particular prostate cancer has been fully described, attention is turned to the current imaging methods with the potential to assess the angiogenesis process and, as a consequence, to detect and localise prostate cancer. As confirmed by all available statistics, cancer represents a major clinical and societal problem in the developed world. The form of cancer with the highest incidence in men is prostate cancer. For prostate cancer, as well as for most forms of cancer, detection of the disease at an early stage is critical to reduce mortality and morbidity. Today, it is well known that pathological angiogenesis represents a crucial step in cancer development and progression. Comparable with most forms of cancer, angiogenesis also plays a fundamental role for prostate cancer growth. As a consequence, angiogenesis is an ideal target not only for novel anti‐angiogenic therapies, but also for modern imaging techniques that aim at cancer localisation by detection of angiogenic microvascular changes. These techniques are mainly based on magnetic resonance, ultrasound, and nuclear imaging. This paper provides a comprehensive review of the available studies on angiogenesis in prostate cancer and its use by modern and emerging imaging techniques for prostate cancer localisation.

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Expression of matrix metalloproteinases (MMP-2 and -9) and their inhibitors (TIMP-1 and -2) in prostate cancer tissue

Cited by 92 publications

References 32 publications

Underexpression of MMP-2 and its regulators, TIMP2, MT1-MMP and IL-8, is associated with prostate cancer

Underexpression of MMP-2 and its regulators, TIMP2, MT1-MMP and IL-8, is associated with prostate cancer

Coordinated peak expression of MMP-26 and TIMP-4 in preinvasive human prostate tumor

Angiogenesis in prostate cancer: onset, progression and imaging

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