Prognostic Values of Matrix Metalloproteinase Family Expression in Human Colorectal Carcinoma

Asano, Tomohiko; Tada, Mitsuhiro; Cheng, Shu; Takemoto, Norihiro; Kuramae, Taro; Abe, Miki; Takahashi, Osamu; Miyamoto, Masaki; Hamada, Junichi; Moriuchi, Tetsuya; Kondo, Satoshi

doi:10.1016/j.jss.2007.02.011

Cited by 70 publications

(71 citation statements)

References 34 publications

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“…The leading current hypothesis is that MMP-15 is involved in cancer progression, as inferable from the reports on the association of MMP-15 with various type of cancer (11)(12)(13). Furthermore, MMP-15 protein has been investigated and proposed as a possible prognostic factor in human colorectal carcinoma (15). Interestingly, our results indicate that the MMP-15 protein is highly expressed in the early stages of colorectal carcinogenesis.…”

Section: Discussionsupporting

confidence: 62%

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Matrix metalloproteinases 15 and 19 are stromal regulators of colorectal cancer development from the early stages

Roncucci¹

2012

Int J Oncol

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Abstract. Matrix metalloproteinases (MMPs) have been well characterized for their ability to degrade extracellular matrix proteins and, thus, they have been studied to elucidate their involvement in both tumor development and progression. In the present study, attention was focused on MMP-15 and MMP-19, two less known members of the MMP family. The expression profile of MMP-15 and -19 was assayed in samples of normal colorectal mucosa, microadenomas and cancer using confocal analysis, western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Both qRT-PCR and western blotting showed that MMP-15 and MMP-19 appeared to be upregulated during colorectal tumorigenesis, with different expression patterns: MMP-15 expression level increases from normal mucosa to microadenomas, with a reduced level in cancer with respect to microadenomas; the semiquantitative immunofluorescence analysis showed a stromal localization of this protein in the early phases of neoplastic transformation. Increasing amount of MMP-19 mRNA and protein levels were observed in the progression of colonic lesions; MMP-19 staining increased in the normal mucosa-microadenoma-carcinoma sequence. Such different expression patterns, are probably due to the different roles played in colorectal tumorigenesis by these two molecules. Conflicting data on the role of these proteins in tumor progression have been reported, thus, an improved understanding of the biological roles of MMPs, in particular the lesser known members such as MMP-15 and 19, in colorectal cancer may lead to a re-evaluation of the use of MMP inhibitors and suggests the need of integrated translational studies on MMP expression patterns. IntroductionMatrix metalloproteinases (MMPs) play a sophisticated role in cancer development due to their abilities to degrade various substrates. MMPs are generally classified as pro-angiogenic factors, since they can degrade the extracellular matrix molecules to facilitate tumor cell migration and invasion (1,2). This concept of the role of MMPs in tumor invasion and metastasis is currently undergoing a major reappraisal most notably as a result of the apparent failure of several 'high-profile' clinical trials of MMP inhibitors in cancer (3).MMP-15 is a recently discovered membrane-type MMP which was originally isolated from a human lung cDNA library, and it consists of a 76-kDa product with 73.9% overall similarity to MMP-14 (4,5). Despite the high degree of structural similarity of these two MMPs, differences in substrate specificity (6,7), as well as tissue or cellular localization, have been demonstrated (8). Although MMP-15 is reported to play a similar role to MMP-14 in cell invasion (9), its implication remains to be elucidated; the importance and role of MMP-14 in promoting tumor growth have been extensively investigated (10), in contrast to the role and function of MMP-15 which is just beginning to be addressed. It has been reported involved in the progression of various kinds of cancers, such as breast, cervical, ...

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Section: Discussionsupporting

confidence: 62%

“…Recent reports indicate MMP-15 as an anti-apoptotic factor in cancer cells (14). Moreover, MMP-15 is also identified as prognostic predictor for disease-free survival in colorectal cancer (15).…”

Section: Introductionmentioning

confidence: 98%

Matrix metalloproteinases 15 and 19 are stromal regulators of colorectal cancer development from the early stages

Roncucci¹

2012

Int J Oncol

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“…MMP-7 is involved in the progression of human rectal cancer and is a key player in invasion and metastasis, and thus, its assessment may become useful for clinical diagnosis and predicting the prognosis of rectal cancer. 20,21 The correlation of MMP-7 expression with liver metastasis has been also reported. 22 It is synergistically upregulated by the oncogenic transcription factors activator protein (AP)-1 and b-catenin.…”

Section: Discussionmentioning

confidence: 94%

“…Cell viability ranged from 84.0% ± 5.5% to 61% ± 6.2% and 34% ± 7.7% following treatment (20,40, and 80 mg/mL, respectively) with RMRE as compared with the control (Figure 2A). There were no significant changes in cell viability after treatment with 5 and 10 mg/mL of RMRE.…”

Section: Effects Of Rmre On Suppressed Tumorassociated Capillary Tubementioning

confidence: 99%

Effects of Monascus-Fermented Rice Extract on Malignant Cell—Associated Neovascularization and Intravasation Determined Using the Chicken Embryo Chorioallantoic Membrane Model

Hsu

et al. 2010

Integr Cancer Ther

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The traditional Chinese medicine, Hong-Qu, also called red mold rice in the United States and Europe, is used for treating blood stasis, a disorder related to hyperlipidemia and atherosclerosis. In addition to improving metabolic syndrome, extracts from Monascus-fermented rice inhibit the proliferation of various cancer cells in vitro and in vivo. The objective was to examine the effect of red mold rice ethanol extract (RMRE) on angiogenesis, invasion, and metastasis during tumor progression. RMRE significantly inhibited the proliferation of SW480 and SW620 human colorectal carcinoma cells in a dose-and time-dependent manner by using the MTT assay. A capillary-like network morphology was observed after the addition of 20 ng/mL vascular endothelial growth factor or SW620 culture-conditional medium, which was not seen after RMRE treatment. Moreover, spontaneous intravasation into Matrigel grafts of SW620 cells from the upper to the lower layers in the chick embryo chorioallantoic membrane (CAM) model was detected by the polymerase chain reaction (PCR) amplification of human Alu genomic DNA from the lower CAMs in the RMRE-untreated group. Neovascularization increased to 75.3% ± 11.6% by SW620 cells onplant with Matrigel grafts in the CAM model. However, RMRE significantly reduced CAM neovascularization in a dose-dependent manner. Finally, RMRE effectively decreased the activity of matrix metalloproteinase (MMP)-7 as determined by reverse transcription PCR (RT-PCR), Western blotting, and casein zymography assays. In summary, Monascus-fermented products exert a potent effect on tumor growth and activation, suggesting that they may serve as supplementary agents in adjuvant cancer therapy.

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“…MMP II is expressed in 71% of esophageal cancer and may be an early event in esophageal tumorigenesis (18). Its expression in colorectal cancer (CRC) is associated with females, distal locations, infiltrative growth patterns and microsatellite stability of the patients (19,20), and even represents a novel expressed tumor associated antigen as the target candidate for CRC immunotherapy (21).…”

Section: Discussionmentioning

confidence: 99%

Knockdown of MMP11 Inhibits Proliferation and Invasion of Gastric Cancer Cells

et al. 2013

Int J Immunopathol Pharmacol

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Matrix metalloproteinase 11(MMPll or stromelysin-3) has recently been reported to playa crucial role in the development and progression of multiple malignancies. The aim of this study was to investigate the function ofMMPll expression in human gastric adenocarcinoma (GAC). Using immunohistochemistry assay, we studied the expression level of MMPll in GAC and adjacent non-cancerous tissues (ANCT). The association between MMPll expression and tumor size and pathological grade, as well as metastatic potential was analyzed. Through small hairpin RNA (shRNA)-mediated MMPll knockdown in SGC-7901 GAC cells, we observed the changes of the biological behaviors of GAC cells. Our results indicated that the rate of positive expression ofMMPll was higher in GAC tissues than in ANCT (55.0% vs 30.0%, P=0.025). MMPll expression had no association with the factors of age or gender of the GAC patients, or the size, pathological staging and lymph node metastases of the tumors (each P>0.05). Furthermore, MMPll knockdown inhibited the proliferative activities and invasive potential of SGC-7901 GAC cells with decreased expression of IGF-l, PCNA and VEGF. Taken together, our findings demonstrated that MMPll expression was increased in GAC tissues, but did not correlate with the clinicopathologic features. Knockdown of MMPll expression could inhibit the proliferation and invasion of GAC cells probably through down-regulation of the IGF-l signaling pathway, suggesting that MMPll might be a potential therapeutic target for the treatment of gastric cancer.Gastric cancer (GC) is a world health burden, ranging as the second cause of cancer death worldwide. The prognosis of gastric cancer is poor with an estimated relative five year survival rate of less than 20% (1). Etiologically, GC arises not only from the combined effects of environmental factors and susceptible genetic variants but also from the accumulation of genetic and epigenetic alterations. Molecular oncobiology studies have brought to light a number of genes that are implicated in gastric carcinogenesis (2).Matrix metalloproteases (MMPs) playa key role in the metabolism of connective tissue proteins in the norm and in pathology. Major MMP subfamilies and matrixins act through promoting the oncogenic transformation of the cells, and angiogenesis (3). MMPs constitute one of the major extracellular matrix degrading enzymic families implicated in cancer development. MMP11 in particular, a member of the matrix metalloproteinases, exhibits collagenolytic function against collagen VI under normal and malignant conditions (4), and is closely related to invasiveness and tumor progression (5). MMP-ll expression is simulated in mouse

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Prognostic Values of Matrix Metalloproteinase Family Expression in Human Colorectal Carcinoma

Cited by 70 publications

References 34 publications

Matrix metalloproteinases 15 and 19 are stromal regulators of colorectal cancer development from the early stages

Matrix metalloproteinases 15 and 19 are stromal regulators of colorectal cancer development from the early stages

Effects of Monascus-Fermented Rice Extract on Malignant Cell—Associated Neovascularization and Intravasation Determined Using the Chicken Embryo Chorioallantoic Membrane Model

Knockdown of MMP11 Inhibits Proliferation and Invasion of Gastric Cancer Cells

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