Expression of matrix metalloproteinases 2, 7 and 9 in patients with colorectal cancer

Kostova, Elena; Slaninka-Miceska, Maja; Labacevski, Nikola; Jakovski, Krume; Trojachanec, Jasmina; Atanasovska, Emilija; Janevski, Vlado; Jovanovik, Rubens; Janevska, Vesna

doi:10.2298/vsp121221024k

Cited by 18 publications

(19 citation statements)

References 29 publications

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“…Several lines of evidence suggest that CAFs are potent initiators of angiogenesis because these cells promote the secretion of MMPs (angiogenic factors) from cancer cells. (19,20) We observed that the mRNA expression of MMP-7 was markedly enhanced (Suppl. Fig.…”

Section: Resultsmentioning

confidence: 98%

“…STAT‐3 signaling induces MMP‐7 expression in PDA cells. Some studies have suggested that MMP‐7 and other MMPs are elevated in human CRC and regulate the angiogenic activity of VEGF in colorectal tissue to promote angiogenesis . Indeed, CAFs induce greater MMP‐7 expression than NFs or PFs can in cancer cells; FGF‐1/‐3 induced MMP‐7 expression both in vitro and in vivo , and inhibiting FGFR4 phosphorylation using PD173074 or FGFR4 silencing reduced MMP‐7 expression.…”

Section: Discussionmentioning

confidence: 99%

“…Some studies have suggested that MMP-7 and other MMPs are elevated in human CRC and regulate the angiogenic activity of VEGF in colorectal tissue to promote angiogenesis. (19,20) Indeed, CAFs induce greater MMP-7 expression than NFs or PFs can in cancer cells; FGF-1 ⁄ -3 induced MMP-7 expression both in vitro and in vivo, and inhibiting FGFR4 phosphorylation using PD173074 or FGFR4 silencing reduced MMP-7 expression. These observations sup-port the hypothesis that CAFs, mediated by FGF signaling, upregulate MMP-7 or directly secrete MMP-7 to drive tumorassociated angiogenesis in colorectal cancer.…”

Section: Discussionmentioning

confidence: 99%

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FGF‐1/‐3/FGFR4 signaling in cancer‐associated fibroblasts promotes tumor progression in colon cancer through Erk and MMP‐7

et al. 2015

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Cancer-associated fibroblasts (CAFs), as the activated fibroblasts in the tumor stroma, are important modifiers of tumour progression. In the present study, we observed that azoxymethane and dextran sodium sulfate treatments induced increasingly severe colorectal mucosal inflammation and the intratumoural accumulation of CAFs. Fibroblast growth factor (FGF)-1 and FGF-3 were detected in infiltrating cells, and FGFR4, the specific receptor for FGF-1 and FGF-3, was detected in colon cancer tissues. The phosphorylation of FGFR4 enhanced the production of metalloproteinase (MMP)-7 and mitogen-activated protein kinase kinase (Mek)/extracellular signal-regulated kinase (Erk), which was accompanied by excessive vessel generation and cell proliferation. Moreover, we separated CAFs, pericarcinoma fibroblasts (PFs), and normal fibroblasts (NFs) from human colon tissue specimens to characterize the function of CAFs. We observed that CAFs secrete more FGF-1/-3 than NFs and PFs and promote cancer cell growth and angiogenesis through the activation of FGFR4, which is followed by the activation of Mek/Erk and the modulation of MMP-7 expression. The administration of FGF-1/-3-neutralizing antibodies or the treatment of cells with FGFR4 siRNA or the FGFR4 inhibitor PD173074 markedly suppressed colon cancer cell proliferation and neovascularization. These observations suggest a crucial role for CAFs and FGF signaling in the initiation and progression of colorectal cancer. The inhibition of the FGF signaling pathway may be a useful strategy for the treatment of colon cancer.

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Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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FGF‐1/‐3/FGFR4 signaling in cancer‐associated fibroblasts promotes tumor progression in colon cancer through Erk and MMP‐7

et al. 2015

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“…Several studies demonstrated that regulation of MMP s secretion leads to the acceleration of tumor invasion [16–19]. MMP -2 and MMP -9 promote the degradation of the extracellular matrix, proliferation [20–22], and invasion of colon cancer cells [23–26]. We hypothesized that, in colon cancer cells, SCRN1 regulates the secretion of MMP s to promote cell proliferation and invasion.…”

Section: Introductionmentioning

confidence: 99%

Secernin-1 Contributes to Colon Cancer Progression through Enhancing Matrix Metalloproteinase-2/9 Exocytosis

Lin

Jiang

et al. 2015

Disease Markers

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Emerging evidence shows that exocytosis plays a key role in tumor development and metastasis. Secernin-1 (SCRN1) is a novel regulator of exocytosis. Our previous work identified SCRN1 as a tumor-associated gene by bioinformatics analysis of transcriptomes. In this study, we demonstrated the aberrant overexpression of SCRN1 at mRNA and protein level in colon cancer. We also revealed that overexpression of SCRN1 was significantly associated with the tumor development and poor prognosis. Experiments in vitro validated that SCRN1 may promote cancer cell proliferation and secretion of matrix metalloproteinase-2/9 (MMP-2/9) proteins to accelerate tumor progression.

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“…Measuring protein expression in the tissue of patients with CRC, Kostova et al (32) noticed that the expression of MMP-9 exhibited a positive correlation with the level of tumor invasion. By contrast, no correlation was detected in the present study between active MMP-2 and the level of tumor invasion.…”

Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinases in Vietnamese patients with colorectal cancer

Bui

Hoang

et al. 2017

Oncology Letters

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Matrix metalloproteinases (MMPs), a family of endopeptidases also known as gelatinases, have been reported to affect the acquisition of the cell proliferative, cell invasive and metastatic phenotype of several types of cancer. In particular, the gelatinases MMP-2 and −9 have been revealed to facilitate tumor growth and invasion in patients with colorectal cancer (CRC). However, it is not known whether the gelatinase activity of MMP-2 and −9 is also elevated in Vietnamese patients with CRC. The activity of MMP-2 and −9 in the tissue samples of 103 patients with CRC was evaluated by gelatin zymography and quantified using ImageJ. The association between the level of activity of MMP-2 and −9 and various clinicopathological factors was analyzed, and Chisio BioPAX Editor software was used to visualize the biological pathways regulating the activity of the MMPs. The present study noticed significantly increased activity of active MMP-2 and MMP-9 in tumor tissues (P<0.01), and significantly decreased levels of pro-form MMP-2 and MMP-9 in tumor tissues (P<0.01), compared with that in adjacent tissues in patients with CRC. A correlation between the normalized different activity of MMP-2 and −9 and various clinicopathological features was observed. Furthermore, bioinformatics analysis indicated that the alteration in the activity of MMP-2 and MMP-9 may have been controlled by biological pathways involving the tissue inhibitors of metalloprotease-2 and −1. These findings indicate that the activity of the gelatinases MMP-2 and −9 affects the tumor progression and metastasis of patients with CRC, providing a potential novel approach for determining the prognosis of CRC.

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Expression of matrix metalloproteinases 2, 7 and 9 in patients with colorectal cancer

Abstract: Immunohistochemical expression of MMPs is a useful indicator of the disease development and progression in patients with colorectal cancer.

Cited by 18 publications

References 29 publications

FGF‐1/‐3/FGFR4 signaling in cancer‐associated fibroblasts promotes tumor progression in colon cancer through Erk and MMP‐7

FGF‐1/‐3/FGFR4 signaling in cancer‐associated fibroblasts promotes tumor progression in colon cancer through Erk and MMP‐7

Secernin-1 Contributes to Colon Cancer Progression through Enhancing Matrix Metalloproteinase-2/9 Exocytosis

Matrix metalloproteinases in Vietnamese patients with colorectal cancer

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