Low Collagenase-1 (MMP-1) and MT1-MMP Expression Levels Are Favourable Survival Markers in Advanced Colorectal Carcinoma

Bendardaf, Riyad; Lamlum, Hanan; Vihinen, Pia; Ristamäki, Raija; Laine, Jukka; Pyrhönen, Seppo

doi:10.1159/000074647

Cited by 30 publications

(17 citation statements)

References 30 publications

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“…Likewise, weak MMP-1 expression has been related to a better prognosis of patients with advanced CRC. 44 However, also our colon cancer patients with high MMP-1 expression showed a tendency towards worse prognosis. Expression of MMP-13 has been associated with poor prognosis in breast cancer 45 and CRC.…”

Section: Discussionmentioning

confidence: 58%

Prognostic significance of matrix metalloproteinases‐1, ‐2, ‐7 and ‐13 and tissue inhibitors of metalloproteinases‐1, ‐2, ‐3 and ‐4 in colorectal cancer

Hilska

Roberts

Collan

et al. 2007

Intl Journal of Cancer

133

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Strong expression of many matrix metalloproteinases (MMPs) has been related to poor survival of colorectal cancer (CRC) patients. The expression of tissue inhibitors of metalloproteinases (TIMPs) has been associated with both a beneficial and a poor outcome and there is thus a need to further clarify the significance of MMPs and TIMPs in CRC. The prognostic significance of 4 MMPs and TIMPs in CRC was evaluated. Formalinfixed, paraffin-embedded tissue arrayed samples of 351 patients with primary colon or rectal cancer of Dukes' stages A-D were selected for immunohistochemical staining of MMP-1, -2, -7 and -13, and TIMP-1, -2, -3 and -4. High expression of MMP-2 in the malignant epithelium as well as in the surrounding stroma was associated with reduced survival of colon cancer patients. Strong epithelial and stromal cytoplasmic staining of TIMP-3 was associated with a longer survival in rectal cancer patients, and here the interobserver variation for evaluating the degree of staining was lower than for epithelial staining. Strong stromal cytoplasmic staining of TIMP-4 predicted longer survival of rectal cancer patients. Multivariate analysis showed that stromal cytoplasmic TIMP-3 staining was the only marker of independent prognostic value. MMP-2 might be a useful prognostic marker in colon cancer, and TIMP-3 and TIMP-4 in rectal cancer, but the findings associated with stromal staining should be interpreted with some caution. Different biologic behavior or different genetic development may explain the differences between colon and rectal cancers regarding the expression of MMP-2, TIMP-3 and TIMP-4. ' 2007 Wiley-Liss, Inc.Key words: colorectal cancer; matrix metalloproteinases; tissue inhibitors of metalloproteinases; prognosis; survival Matrix metalloproteinases (MMPs) are a large family of zincdependent neutral endopeptidases that play an important role in the degradation of all matrix components crucial for malignant tumor growth, invasion and metastasis. 1,2 Metalloproteinases are inhibited by tissue inhibitors (TIMPs) which are secreted proteins. These bioactive substances are specific inhibitors of MMPs that bind to enzymatically active MMPs at a 1:1 molar stoichiometry thus inhibiting proteolysis. 3 The role of TIMPs for the homeostasis of the extracellular matrix is critical and may inhibit or stimulate tumorigenesis. 4 Many studies have shown that the expression of several MMPs is enhanced in a number of malignancies, including colorectal cancer (CRC), but the relation between the expression of MMPs and overall patient survival is not clear. 5,6 Enhanced expression of MMP-1, -7 and -13 has been reported to be associated with metastasis and poor survival of patients with CRC. 7-9 Tissue concentrations of MMP-1, MMP-2 and TIMP-1 are increased in CRC compared to healthy colorectal tissue. This has been related to the role of these endogenous substances in cancer progression. 2 Healthy tissue may contain high levels of TIMP-2 10 and the levels of TIMP-3 mRNA are regionally increased in moderately and poorl...

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Section: Discussionmentioning

confidence: 58%

Prognostic significance of matrix metalloproteinases‐1, ‐2, ‐7 and ‐13 and tissue inhibitors of metalloproteinases‐1, ‐2, ‐3 and ‐4 in colorectal cancer

Hilska

Roberts

Collan

et al. 2007

Intl Journal of Cancer

133

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“…That MMP-1 inhibition increases the rate of apoptosis may explain previous reports that blocking of MMP-1 activity by TIMP-1 inhibits apoptosis, 38 that increased expression of this enzyme leads to tumor progression and metastasis, 34 and that low levels of MMP-1 are favorable markers for tumor spreading. 39 The rate of apoptosis in a tumor determines its growth, invasion, and metastasis and in nearly all instances a significant correlation between expression of MMP-1 and cancer survival has been documented. 34,39 -41 Because control of cell survival may be achieved through inhibition of apoptosis, it is possible that this is another mechanism by which MMP-1 promotes cell invasion and growth in inflammatory, angiogenic, and tumoral processes.…”

Section: Discussionmentioning

confidence: 99%

Matrix Metalloproteinase-1 Associates with Intracellular Organelles and Confers Resistance to Lamin A/C Degradation during Apoptosis

Limb

Matter

Murphy

et al. 2005

The American Journal of Pathology

109

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Matrix metalloproteinase (MMP)-1, commonly known as collagenase-1, and able to cleave interstitial collagens, 1 is produced by various types of cells in vitro and in vivo and its expression has been associated to inflammation, wound healing, and tumor invasion, growth, and metastasis. [2][3][4] Although the main role ascribed to MMPs has been the degradation of extracellular matrix for facilitation of cell division, migration, and differentiation, more recent work has provided evidence for the role of these enzymes in targeting nonmatrix substrates, such as cell bound cytokines, enzymes, and cell surface receptors. 5,6 It has been further suggested that there may still be more unknown substrates for these enzymes. 6 Evidence for the role of various MMPs in mediating cell functions has been given by the demonstration that gelatinases A and B (MMP-2 and MMP-9) modulate cell proliferation and differentiation, 7,8 and that inhibition of MMPs by natural inhibitors of matrix metalloproteinases (TIMPs) have diverse effects on proliferation and apoptosis in various cell types. For example, TIMPs-1 and -2 may exhibit growth factor-like activity, 9,10 while TIMP-1 can also inhibit tumor cell growth. 11 Although most MMPs are secreted and activated extracellularly, some have been shown to be anchored to the cell surface by a transmembrane domain (MT1-, MT2-, MT3-, and MT5-MMPs) and to contain a short cytoplasmic tail at the C-terminal region of the protein that facilitates their interaction with intracellular proteins that regulate cell function. 12 Furthermore, intracellular MMP-1 in platelets has been shown to activate pathways that signal phosphorylation of intracellular proteins, distributes ␤ 3 integrins to cell contact points, and primes these cells for aggregation. This provides new evidence that MMP-1 can regulate outside-in signaling events that control cell function and phenotype. 13 In addition to platelets, intracellular localization of MMP-1 has been documented in various cells, including human vascular endothelium 14 and rabbit synovial fibroblasts cultured in the presence of anti-␣5 integrin antibodies.

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“…Low expression levels of MT1-MMP are considered as favorable survival markers in advanced colorectal carcinoma (Bendardaf et al, 2003). MT1-MMP has been detected in tumor cells and adjacent stromal cells in a variety of human tumors, including breast, cervical, colon, bladder, gastric, glioma, pancreatic, liver, ovarian, prostate and thyroid cancer Zucker et al, 2003).…”

Section: Biological Featuresmentioning

confidence: 99%

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Sbardella

Fasciglione

Gioia

et al. 2012

Molecular Aspects of Medicine

210

212

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a b s t r a c tHuman matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases. They are ubiquitarian enzymes, structurally characterized by an active site where a Zn 2+ atom, coordinated by three histidines, plays the catalytic role, assisted by a glutamic acid as a general base. Various MMPs display different domain composition, which is very important for macromolecular substrates recognition. Substrate specificity is very different among MMPs, being often associated to their cellular compartmentalization and/or cellular type where they are expressed. An extensive review of the different MMPs structural and functional features is integrated with their pathological role in several types of diseases, spanning from cancer to cardiovascular diseases and to neurodegeneration. It emerges a very complex and crucial role played by these enzymes in many physiological and pathological processes.

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Low Collagenase-1 (MMP-1) and MT1-MMP Expression Levels Are Favourable Survival Markers in Advanced Colorectal Carcinoma

Cited by 30 publications

References 30 publications

Prognostic significance of matrix metalloproteinases‐1, ‐2, ‐7 and ‐13 and tissue inhibitors of metalloproteinases‐1, ‐2, ‐3 and ‐4 in colorectal cancer

Prognostic significance of matrix metalloproteinases‐1, ‐2, ‐7 and ‐13 and tissue inhibitors of metalloproteinases‐1, ‐2, ‐3 and ‐4 in colorectal cancer

Matrix Metalloproteinase-1 Associates with Intracellular Organelles and Confers Resistance to Lamin A/C Degradation during Apoptosis

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

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