Study of matrix metalloproteinases and their inhibitors in prostate cancer

Abstract

BACKGROUND: Extracellular matrix metalloproteases (MMPs) have raised an extraordinary interest in cancer research because of their potential role in basal membrane and extracellular matrix degradation, consequently facilitating tumour invasion and metastases development. METHODS: An immunohistochemical study was performed using tissue arrays and specific antibodies against MMPs 1, 2, 7, 9, 11, 13, 14, and their tissue inhibitors, TIMPs 1, 2 and 3. More than 2600 determinations on cancer specimens from 133 patients with clinically localised prostate carcinoma, 20 patients with prostatic intraepithelial neoplasia and 50 patients with benign prostate hyperplasia and controls, were performed. RESULTS: When compared with benign pathologies, prostate carcinomas had higher expression of all MMPs and TIMPs. Dendogram shows a first-order division of tumours into two distinct MMPs/TIMPs molecular profiles, one of them with high MMPs/TIMs expression profile (n ¼ 70; 52.6%). Tumours with high expression of MMP-11 or -13, or cluster thereof, were significantly associated with higher probability of biochemical recurrence. The prevalence of prostate cancer is so high that it could be considered as a normal age-related phenomenon (Hughes et al, 2005). Several published autopsy series have shown that up to one-third of men between the ages of 30 and 40 years harbour histological evidence of prostate carcinoma (Sakr et al, 1994).A significant minority of patients undergoing radical prostatectomy for clinical organ-confined disease will ultimately be found to have pathological evidence of spread outside the prostate. Although these patients may be expected to have progression and survival rates comparable to those of patients with clinical advanced clinical disease, as defined by grade and serum prostatespecific antigen (PSA) level, those men who present with clinical stage T3 are likely to have greater tumour volume, higher grade and increased likelihood of regional spread. Currently, the majority of men undergoing prostatectomy for pathologically advanced disease are categorised as high risk on the basis of serum PSA value or biopsy Gleason score. Nevertheless, there is some overlap in the groups of men undergoing radical prostatectomy for clinical stage T3 and for pathological stage T3 (Meng and Carrol, 2007).Despite recent improvement in diagnostic and therapeutic techniques, the survival rate of prostate cancer patients remains poor due to post-treatment recurrence disease. Despite all the recent efforts in the identification of molecular mechanisms involved in the progression of prostate cancer, tumour progression in the prostatic compartment, as well as in the metastasis compartment, is poorly understood (Logothetis and Lin, 2005). These pitfalls underscore the need for new risk markers that allow the early detection of carcinogenesis and, therefore, of cancer relapse.Degradation of the stromal connective tissue and basement membrane components are key elements in tumour invasion and metastasis. This is particularly true wi...

Unripe Rubus coreanus Miquel suppresses migration and invasion of human prostate cancer cells by reducing matrix metalloproteinase expression

“…25) Conversely, knocking down MMP-2 and MMP-9 genes was found to decrease tumor invasion, migration, metastasis, and angiogenesis in glioblastoma and prostate cancer cells. [26][27][28][29] TIMPs inhibit the activity of MMP-2 and MMP-9.…”

Angiogenesis in prostate cancer: onset, progression and imaging

“…An association between MMPs and/or TIMPs expression and parameters indicative of prostate cancer aggressiveness has also been reported. Recently, Escaff et al [ 56 ] reported that MMPs/TIMPs expressions are in general higher in prostate cancer than in prostate benign tissue, confi rming the important role of these factors in the molecular biology of prostate cancer.…”

Matrix metalloproteinases 2 and 9 expression in canine normal prostate and with proliferative disorders

“…In the same manner, BREHMER et al (2003), ZHONG et al (2008 observed higher expression of MMP-2 and MMP-9 in neoplastic human prostate than in normal ones or with BPH, respectively. Besides, ESCAFF et al (2010) found higher expression of different types of MMP and TIMP in human prostates with carcinoma than in glands with benign changes, concluding that such enzymes have an important role in the molecular biology of prostatic carcinomas.…”