Selected Matrix Metalloproteinases (MMP-2, MMP-7) and Their Inhibitor (TIMP-2) in Adult and Pediatric Cancer
Abstract
1. Introduction
2. MMP—Characteristic and Classification
3. TIMPs—Characteristic and Classification
4. The Involvement of Metalloproteinases and Their Inhibitors in Cancer
4.1. Adult Population—The Involvement of MMPs and TIMP
4.1.1. MMP-2 Involvement in Cancer
4.1.2. TIMP-2 Dual Role in Cancer
4.1.3. MMP-2/TIMP-2 Imbalance in Cancer
4.1.4. MMP-7 Involvement in Cancer
4.2. Pediatric Cancer and MMP-2, MMP-7, and TIMP-2 Involvement
5. Summary
Author Contributions
Funding
Conflicts of Interest
References
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Collagenases | Gelatinases | Stromelysins | |||
---|---|---|---|---|---|
MMP-1 | Collagenase-1 Interstitial collagenase | MMP-2 | Gelatinase A 72-kDa type IV collagenase | MMP-3 | Stromelysin-1 |
MMP-8 | Collagenase-2 Neutrophil collagenase | MMP-9 | Gelatinase B | MMP-10 | Stromelysin-2 |
MMP-13 | Collagenase-3 | MMP-11 | Stromelysin-3 | ||
Matrilysins | Membrane-Type MMPs | Other MMPs | |||
MMP-7 | Matrilysin | MMP-14 | Membrane type-1 MMP | MMP-12 | Macrophage metallo-elastase |
MMP-26 | Matrilysin-2/endometase | MMP-15 | Membrane type-2 MMP | MMP-20 | Enamelysin |
MMP-16 | Membrane type-3 MMP | MMP-28 | Epilysin | ||
MMP-17 | Membrane type-4 MMP | ||||
MMP-24 | Membrane type-5 MMP | ||||
MMP-25 | Membrane type-6 MMP |
MMP/TIMP | Type of the Cancer | Type of the Sample | Main Findings | References |
---|---|---|---|---|
MMP-2 | Colorectal cancer | Tumor tissue Plasma | Increased concentration of MMP-2 in tumor tissue, compared with tumor-free tissue MMP-2 plasma level was distinctly elevated in patients with lymph node metastasis compared with those without | Langenskiold et al. [44] |
Tumor tissue | High expression of MMP-2 in cancer cells was associated with decreased survival of colon cancer patients | Hilska et al. [45] | ||
Ovarian cancer | Tumor tissue | Significant relationship between activated MMP-2 and invasiveness, metastasis, disease progression; MMP-2 as a potential marker of prognosis | Wu et al. [46] | |
Ovarian tumors /peritoneal implants | MMP-2 overexpression by cancer cells in peritoneal implants and not in the primary ovarian cancer is predictive of ovarian cancer prognosis | Peringy et al. [47] | ||
Breast cancer | Tumor tissue | The ratio of active to total MMP-2 was increased in high-grade tumors | Davies et al. [48] | |
Tumor tissue | Activation of pro-MMP-2 may be an indicator of lymph node metastasis in breast cancer | Iwata et al. [49] | ||
Tumor tissue | Decreased MMP-2 concentration could serve as a marker for favorable prognosis in breast cancer | Talvensaari-Mattila et al. [50] | ||
Prostate cancer | Plasma | The level of MMP-2 increased in patients with metastatic prostate cancer compared to BPH/healthy patients | Morgia et al. [51] | |
Bladder cancer | Urine | Urinary excretion of MMP-2 is associated with higher stage and grade; it may indicate tumor progression and predict relapse of the disease | Gerhards et al. [52] | |
Tumor tissue | Levels of active MMP-2 increased with tumor grade and invasiveness | Davies et al. [53] | ||
Central nervous system malignancies | CSF | All patients with positive CSF cytologies had activated MMP-2 | Friedberg et al. [54] | |
Tumor tissue | Expression of MMP-2 significantly upregulated in malignant gliomas and correlated with progression of human gliomas | Sawaya et al. [55] | ||
Lung adenocarcinoma | Tumor tissue | MMP-2 positive patients had poorer prognosis | Kodate et al. [56] | |
Pancreas cancer | Tumor tissue | MMP-2 plays an important role in tumor cell invasion and leads to progression of the disease | Ellenrieder et al [57]. | |
Primary skin melanoma | Tumor tissue | MMP-2 positive patients had poorer prognosis | Vaisanen et al. [58] | |
MMP-2/TIMP-2 | HCC | Serum + tumor tissue | MMP-2/TIMP-2 imbalance (and particularly TIMP-2 levels), could become a valuable prognostic factor in patients with HCC | Gianelli et al. [59] |
Cervical carcinoma | Tumor tissue | Presence of mRNA for both MMP-2 and TIMP-2 is associated with poor survival | Davidson et al. [60] | |
Serum | Medium level of TIMP-2 and MMP-2/TIMP-2 complex in serum is higher in healthy women, compared to those with a malignant tumor | Talvensaari-Mattila et al. [61] | ||
Oral cancer | Tumor tissue | A rate of MMP-2/TIMP-2 complex expression is better for characterization of MMP-2 activity | Shretsha et al. [62] | |
Bladder cancer | Tumor tissue | The expression of MMP-2 and TIMP-2 was higher in invasive tumors, and was strongly associated with poorer survival | Kanayama et al [63]. |
Type of Cancer | Type of Sample | Result | Study |
---|---|---|---|
Esophageal cancer | Tumor tissue | Overexpression of MMP-7 is strictly connected with higher TNM stage, higher invasive grade, presence of lymph nodes metastasis | Miao et al. (meta-analysis) [71] |
Gastric cancer | Tumor tissue | Overexpression of MMP-7 predicts presence of lymph node metastasis | Okayama et al. [72] |
Tumor tissue | MMP-7 levels are higher in gastric cancer with vascular invasion compared to the group without invasion | Yamashita et al. [73] | |
Colorectal cancer | Serum | MMP-7 is an independent prognostic factor for survival in advanced colorectal cancer, possibly even more accurate than LDH | Maurel et al. [74] |
Serum + Tumor tissue | Overexpression of MMP-7 in advanced cancer, compared to non-metastatic disease Higher level of MMP-7 in serum of stage III/IV patients, compared to patients in I/II stage disease | Polistena et al. [75] | |
Pancreatic cancer | Tumor tissue | MMP-7 positivity was correlated with poor prognosis | Yamamoto et al. [76] |
Tumor tissue | MMP-7 level was significantly increased in pancreatic cancer compared with healthy pancreas, and was related with reduced survival | Jones et al. [77] | |
Plasma + Pancreatic juice | Median plasma MMP-7 levels were significantly higher in carcinoma, compared with chronic pancreatitis Combined MMP-7 and Ca 19-9 levels in plasma give positive predictive value of 100% | Kuhlmann et al. [78] | |
Ovarian cancer | Tumor tissue | Overexpression of MMP-7 in high-grade ovarian cancer and low malignant potential ovarian tumors; absence of MMP-7 expression in healthy ovary | Tanimoto et al. [79] |
NSCLC | Tumor tissue | Overall survival significantly lower in patients with overexpression of MMP-7 | Liu et al. [80] |
Bladder cancer | Tumor tissue + serum | Overexpression of MMP-7 in tissue samples of metastatic bladder cancer, compared to those with localized disease High tissue expression levels are accompanied by elevated serum MMP-7 concentration | Szarvas et al. [81] |
MMP/TIMP | Type of Cancer | Type of Sample | Result | Study |
---|---|---|---|---|
MMP-2 | Acute lymphoblastic leukemia | bone marrow | In pediatric cases positive MMP-2 expression was in relationship with high-risk tumor group and T-cell immunophenotype | Kuittinen et al. [83] |
Acute myelogenous leukemia | adult cell-lines | Inhibiting the activity of MMP-2 significantly reduced invasiveness of leukemic cells | Sawicki et al. [84] | |
Central nervous system tumors | tumor tissue | Distinctly positive expression of MMP-2 in anaplastic astrocytoma and glioblastoma compared with healthy brain and low-grade astrocytoma tissue | Gu et al. [85] | |
Alveolar (ARMS) and embryonal (ERMS) rhabdomyosarcoma | ARMS and ERMS cell lines | ARMS cell line with increased expression of MMP-2 was more invasive compared to ERMS cell line with low levels of MMP-2. | Onisto et al. [86] | |
ARMS and ERMS tumor samples | ARMS showed stronger MMP-2 expression, compared with ERMS type | Diomedi-Camassei et al. [87] | ||
Osteosarcoma | cell lines | The most invasive cell line contained the highest amounts of MMP-2 | Bjorland et al. [88] | |
MMP-2/TIMP-2 | Lymphomas | Plasma | Newly diagnosed lymphoma patients had higher levels of MMP-2/TIMP-2 complex and lower levels of TIMP-2, compared to healthy individuals Patients with highest plasma levels of MMP-2/TIMP-2 complex had a greater chance for relapse of the disease | Pennanen et al. [89] |
Neuroblastoma | Tumor tissue | Higher levels of MMP-2 mRNA and the ratio of MMP-2/TIMP-2 mRNA were observed in advanced stages and in patients who died from the progression of the disease | Ara et al. [90,91] | |
Tumor tissue | Higher levels of MMP-2 in stage IV compared to stage I and II | Sugiura et al. [92] | ||
Tumor tissue | Expression of MMP-2 was increased in advanced stages of the disease | Ribatti et al. [93] | ||
Retinoblastoma (RB) | Tumor tissue | MMP-2 and TIMP-2 were overexpressed in invasive tumors | Adithi et al. [94] | |
Cell lines | Higher expression of MMP-2 in poorly differentiated RB compared with moderately/well-differentiated RB Using inhibitors of MMP-2 and MMP-9 results in reduction in cell line migration ability, and significant decrease of cell viability | Webb et al. [95] | ||
Neuroblastoma RhabdomyosarcomaOsteosarcoma | Cell lines | In neuroblastoma in more aggressive cell lines, MMP-2 expression was twice as high as in less aggressive cells The highest level of MMP-2 was determined for osteosarcoma cell line In neuroblastoma, TIMP-2 was overexpressed in less aggressive line, compared with expression in more aggressive cell line | De Veas et al. [96] | |
TIMP-2 | Lymphomas | Tumor tissue | TIMP-2 expression exclusively in lymphomas, none in reactive lymph nodes | Stolarska et al. [97] |
Hodgkin lymphoma | Tumor tissue | TIMP-2 expression correlate with systemic symptoms | Pennanen et al. [98] | |
MMP-7 | Acute myelogenous leukemia | Cell lines | Only more aggressive cells expressed MMP-7 By inhibiting MMP-7 40% reduction of invasiveness was revealed | Lynch et al. [99] |
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Kaczorowska, A.; Miękus, N.; Stefanowicz, J.; Adamkiewicz-Drożyńska, E. Selected Matrix Metalloproteinases (MMP-2, MMP-7) and Their Inhibitor (TIMP-2) in Adult and Pediatric Cancer. Diagnostics 2020, 10, 547. https://doi.org/10.3390/diagnostics10080547
Kaczorowska A, Miękus N, Stefanowicz J, Adamkiewicz-Drożyńska E. Selected Matrix Metalloproteinases (MMP-2, MMP-7) and Their Inhibitor (TIMP-2) in Adult and Pediatric Cancer. Diagnostics. 2020; 10(8):547. https://doi.org/10.3390/diagnostics10080547
Chicago/Turabian StyleKaczorowska, Aleksandra, Natalia Miękus, Joanna Stefanowicz, and Elżbieta Adamkiewicz-Drożyńska. 2020. "Selected Matrix Metalloproteinases (MMP-2, MMP-7) and Their Inhibitor (TIMP-2) in Adult and Pediatric Cancer" Diagnostics 10, no. 8: 547. https://doi.org/10.3390/diagnostics10080547
APA StyleKaczorowska, A., Miękus, N., Stefanowicz, J., & Adamkiewicz-Drożyńska, E. (2020). Selected Matrix Metalloproteinases (MMP-2, MMP-7) and Their Inhibitor (TIMP-2) in Adult and Pediatric Cancer. Diagnostics, 10(8), 547. https://doi.org/10.3390/diagnostics10080547