A PSP94-derived Peptide PCK3145 inhibits MMP-9 Secretion and Triggers CD44 Cell Surface Shedding: Implication in Tumor Metastasis

Annabi, Borhane; Bouzeghrane, Mounia; Currie, Jean-Christophe; Hawkins, Robert E.; Dulude, Hélène; Daigneault, Luc; Ruiz, Marcia T.; Wiśniewski, Jan; Garde, Seema V.; Rabbani, Shafaat A.; Panchal, Chandra J.; Wu, Jinzi J.; Béliveau, Richard

doi:10.1007/s10585-005-2669-1

Cited by 36 publications

(29 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The tumor suppressor PSP94, also known as b-microseminoprotein or prostatic inhibin, is a small (10.7 kDa), non-glycosylated and cysteine-rich protein that is abundantly secreted by the prostate gland and is found in both seminal fluid and blood (Garde et al, 1999;Shukeir et al, 2003;Annahi et al, 2005;Lamy et al, 2006). It is not known how the expression of the PSP94-encoding MSMB gene is regulated.…”

Section: Introduction Results and Discussionmentioning

confidence: 99%

“…The molecular basis for the tumor-suppressor function of PSP94 is complex as this protein has been found to promote tumor cell apoptosis (Garde et al, 1999), to inhibit the secretion of a matrix metalloproteinase that is implicated in tumor metastasis (Annahi et al, 2005), and to decrease tumor-associated, vascular endothelial growth factor (VEGF)-mediated vascularization (Lamy et al, 2006). Interestingly, the antitumor effects of PSP94 can be recapitulated with a synthetic peptide comprising an N-terminal fragment of PSP94 and this peptide is currently clinically tested for the treatment of metastatic prostate cancer (Shukeir et al, 2004;Annahi et al, 2005;Lamy et al, 2006).…”

Section: Introduction Results and Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The gene encoding the prostatic tumor suppressor PSP94 is a target for repression by the Polycomb group protein EZH2

et al. 2007

View full text Add to dashboard Cite

BelgiumPSP94, for prostatic secretory protein of 94 amino acids, is secreted by the prostate gland and functions as a suppressor of tumor growth and metastasis. The expression of PSP94 is lost in advanced, hormone-refractory prostate cancer and this correlates with an increased expression of the Polycomb protein EZH2 (enhancer of zeste homolog 2), which represses transcription via trimethylation of histone H3 on Lys27 (H3K27). We show here that these events are causally related and that the MSMB gene, which encodes PSP94, is trimethylated on H3K27 in androgen-refractory, but not in androgensensitive prostate cancer cells. Chromatin immunoprecipitation experiments confirmed an association of EZH2 with the MSMB gene. The RNAi-mediated knockdown of EZH2 resulted in a loss of H3K27 trimethylation and an increased expression of the MSMB gene. Conversely, the overexpression of EZH2 was associated with a decreased expression of the MSMB gene. We also demonstrate that MSMB is additionally repressed in androgen-refractory prostate cancer cells by the hypoacetylation of histone H3K9 and the hypermethylation of a CpG island in the promoter region. Our data disclose a hitherto unexplored link between the putative oncogene EZH2 and the tumor suppressor PSP94, and show that MSMB is silenced by EZH2 in advanced prostate cancer cells.

show abstract

Section: Introduction Results and Discussionmentioning

confidence: 99%

Section: Introduction Results and Discussionmentioning

confidence: 99%

The gene encoding the prostatic tumor suppressor PSP94 is a target for repression by the Polycomb group protein EZH2

et al. 2007

View full text Add to dashboard Cite

show abstract

“…It was surprising therefore, to find that the fraction of MSMB-positive cells fell to 10% before the expression correlated with a negative outcome, suggesting that there is a redundancy in protein expression and a fraction of MSMB-expressing cells may be sufficient to maintain any potential tumor suppressing effect(s) that MSMB may exert on tumor cells. Using exogenous MSMB, in vitro and in vivo studies indicate that MSMB may have several antitumor effects on prostate tumor cells, such as suppressing growth and inducing apoptosis; [36][37][38] decreasing metastatic disease, [39][40][41] and inhibiting angiogenesis. 42 Recently, MSMB has gained further attention as a candidate for prostate cancer susceptibility gene, 20,21 and several causal risk alleles affecting the level of gene transcription have been identified in the region upstream of the coding sequence.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the prognostic significance of MSMB and CRISP3 in prostate cancer using automated image analysis

et al. 2011

View full text Add to dashboard Cite

Despite prostate cancer being the most frequent cancer in men in the Western world, tissue biomarkers for predicting disease recurrence after surgery have not been incorporated into clinical practice. Our group has previously identified b-microseminoprotein (MSMB) and cysteine-rich secretory protein-3 (CRISP3) as independent predictors of biochemical recurrence after radical prostatectomy. The purpose of the present study was to use automated image analysis, enabling quantitative determination of MSMB and CRISP3 expressions in a large cohort and to validate the previous findings. MSMB and CRISP3 protein expressions were assessed on tissue microarrays constructed from 3268 radical prostatectomy specimens. Whole-slide digital images were captured, and a novel cytoplasmic algorithm was used to develop a quantitative scoring model for cytoplasmic staining. Classification regression tree analysis was used to group patients, with different risk for biochemical recurrence, depending on level of protein expression. Patients with tumors expressing high levels of MSMB had a significantly reduced risk for biochemical recurrence after radical prostatectomy (HR ¼ 0.468; 95% CI 0.394-0.556; Po0.001). Multivariate analysis adjusted for clinicopathological parameters revealed that MSMB expression was an independent predictor of decreased risk of recurrence (HR ¼ 0.710; Po0.001). We found no correlation between CRISP3 expression and biochemical recurrence. In this current study, we applied a novel image analysis on a large independent cohort and successfully verified that MSMB is a strong independent factor, predicting favorable outcome after radical prostatectomy for localized prostate cancer.

show abstract

“…271 Other studies in cancer cells showed that CD44 captures MMP-2 and MMP-9 at the tumor cell surface, where MMPs then locally digest the ECM surrounding the tumor cells during extravasation. 272,273 Other MMPs might also contribute to ECM proteolysis. While conclusive in vivo proof in support of this is still missing, there are many findings that point in this direction.…”

Section: Brain Cancermentioning

confidence: 99%

Matrix metalloproteinases in the brain and blood–brain barrier: Versatile breakers and makers

Rempe

Hartz

Bauer

2016

J Cereb Blood Flow Metab

523

422

View full text Add to dashboard Cite

Matrix metalloproteinases are versatile endopeptidases with many different functions in the body in health and disease. In the brain, matrix metalloproteinases are critical for tissue formation, neuronal network remodeling, and blood-brain barrier integrity. Many reviews have been published on matrix metalloproteinases before, most of which focus on the two best studied matrix metalloproteinases, the gelatinases MMP-2 and MMP-9, and their role in one or two diseases. In this review, we provide a broad overview of the role various matrix metalloproteinases play in brain disorders. We summarize and review current knowledge and understanding of matrix metalloproteinases in the brain and at the bloodbrain barrier in neuroinflammation, multiple sclerosis, cerebral aneurysms, stroke, epilepsy, Alzheimer's disease, Parkinson's disease, and brain cancer. We discuss the detrimental effects matrix metalloproteinases can have in these conditions, contributing to blood-brain barrier leakage, neuroinflammation, neurotoxicity, demyelination, tumor angiogenesis, and cancer metastasis. We also discuss the beneficial role matrix metalloproteinases can play in neuroprotection and anti-inflammation. Finally, we address matrix metalloproteinases as potential therapeutic targets. Together, in this comprehensive review, we summarize current understanding and knowledge of matrix metalloproteinases in the brain and at the blood-brain barrier in brain disorders.

show abstract

A PSP94-derived Peptide PCK3145 inhibits MMP-9 Secretion and Triggers CD44 Cell Surface Shedding: Implication in Tumor Metastasis

Cited by 36 publications

References 55 publications

The gene encoding the prostatic tumor suppressor PSP94 is a target for repression by the Polycomb group protein EZH2

The gene encoding the prostatic tumor suppressor PSP94 is a target for repression by the Polycomb group protein EZH2

Evaluation of the prognostic significance of MSMB and CRISP3 in prostate cancer using automated image analysis

Matrix metalloproteinases in the brain and blood–brain barrier: Versatile breakers and makers

Contact Info

Product

Resources

About