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The role of matrix metalloproteinases in pathogenesis, diagnostics, and treatment of human prostate cancer

Tomasz Wiśniowski
Tomasz Wiśniowski
, 
Jarosław Bryda
Jarosław Bryda
 y 
Sławomir Wątroba
Sławomir Wątroba
   | 01 mar 2023
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Article Category: Review
Publicado en línea: 01 mar 2023
Páginas: 9 - 20
Recibido: 26 feb 2022
Aceptado: 15 nov 2022
DOI: https://doi.org/10.2478/ahem-2023-0002
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© 2023 Tomasz Wiśniowski et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Figure 1

Diagram of the tumor microenvironment in prostate cancer [74, modified]
Diagram of the tumor microenvironment in prostate cancer [74, modified]

The TNM classification of prostate cancer [19]

The TNM classification
T - Primary tumor (stage based on DRE only)
TX - Primary tumor cannot be assessedT0 - No evidence of primary tumorT1 - Clinically inapparent tumor that is not palpableT1a - Tumor incidental histological finding in 5% or less of tissue resectedT1b - Tumor incidental histological finding in more than 5% of tissue resectedT1c - Tumor identified by needle biopsy (because of elevated PSA)T2 - Tumor that is palpable and confined within the prostateT2a - Tumor involves one half of one lobe or lessT2b - Tumor involves more than half of one lobe, but not both lobesT2c - Tumor involves both lobesT3 - Tumor extends through the prostatic capsuleT3a - Extracapsular extension (unilateral or bilateral)T3b - Tumor invades seminal vesiclesT4 - Tumor is fixed or invades adjacent structures other than seminal vesicles: external sphincter, rectum, levator muscles and/or pelvic wall
N - Regional Lymph Nodes
NX - Regional lymph nodes cannot be assessedN0 - No regional lymph node metastasisN1 - Regional lymph node metastasis
M - Distant Metastasis
M0 - No distant metastasisM1 - Distant metastasisM1a - Non-regional lymph nodesM1b - BonesM1c - Other sites
DRE – digital rectal examination; PSA – prostate-specific antigen; TNM – tumor-node-metastasis

The risk of biochemical recurrence of limited and locally advanced prostate cancer [18]

Definition
Low-risk Intermediate-risk High-risk
PSA < 10 ng/ml, GS < 7 (ISUP grade 1), cT1-2a PSA 10–20 ng/ml, GS 7 (ISUP grade 2/3), cT2b PSA > 20 ng/ml, GS > 7 (ISUP grade 4/5), cT2c any PSAany GS (any ISUP grade)cT3-4 or cN+
Localized Locally advanced
GS– Gleason score; ISUP – International Society for Urological Pathology; PSA – prostate-specific antigen

Matrix metalloproteinases and their substrates [26]

Matrix metalloproteinases Name Substrates
MMP-1 collagenase 1 collagen type I, II, III, V, VII, VIII, X gelatine, entactin, aggrecan
MMP-2 gelatinase A collagen type I, IV, V, VII, X, XI, XIV, gelatine, elastin, fibronectin, laminin, aggrecan
MMP-3 stromelysin 1, proteoglycanase collagen type III, IV, V, IX, X, XI, elastin, laminin, fibronectin, aggrecan, gelatine, proMMP-1, -8, -9
MMP-7 matrilysin, metalloendopeptidase collagen type IV, X, gelatine, laminin
MMP-8 collagenase 2 collagen type I, II, III, V, VII, VIII, X, proteoglycans, fibronectin
MMP-9 gelatinase B collagen type IV, V, VII, X, XIV, gelatine, aggrecan, elastin, entactin, fibronectin
MMP-10 stromelysin 2 collagen type III, IV, V, gelatine, casein, elastin, laminin, aggrecan, fibronectin
MMP-11 stromelysin 3 collagen type IV, fibronectin, laminin, aggrecan, casein, gelatine
MMP-12 elastase, macrophage metaloelastase collagen type IV, elastin, gelatine, fibronectin, vitronectin, laminin
MMP-13 collagenase 3 collagen type I, II, III
MMP-14 MT1-MMP collagen type III, gelatine, fibronectin, vitronectin, aggrecan, perlecan, laminin, tenascin
MMP-15 MT2-MMP aggrecan, perlecan, laminin, bronectin, tenascin, nidogen
MMP-16 MT3-MMP collagen type III, gelatine
MMP-17 MT4-MMP cytokines precursors
MMP-18 collagenase 4 collagen type I, II, III
MMP-20 enamelysin amelogenin
MMP-23 CA-MMP -
MMP-24 MT5-MMP proMMP-2, -13
MMP-25 MT6-MMP proMMP-2
MMP-26 matrilysin, endometase -
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Life Sciences, Molecular Biology, Microbiology and Virology, Medicine, Basic Medical Science, Immunology
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