The influence of MMP-14, TIMP-2 and MMP-2 expression on breast cancer prognosis

Têtu, Bernard; Brisson, Jacques; Wang, Chang Shu; Lapointe, Hélène; Beaudry, Guillaume; Blanchette, Caty; Trudel, Dominique

doi:10.1186/bcr1503

Cited by 124 publications

(89 citation statements)

References 50 publications

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“…In women with breast cancer, the MT1-MMP mRNA, extracted from tumor or stromal cells, is an independent predictive indicator of overall survival (38,39). Peritumoral lymphovascular invasion correlates with distant metastasis and is also an independent prognostic factor of overall survival in node-negative breast cancer (40,41).…”

Section: Cancer Cell Mt1-mmp Downregulation Reduces the Number Of Migmentioning

confidence: 99%

Cancer Cell–Associated MT1-MMP Promotes Blood Vessel Invasion and Distant Metastasis in Triple-Negative Mammary Tumors

Perentes

Kirkpatrick²,

Nagano³

et al. 2011

Cancer Research

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Functional roles for the cancer cell-associated membrane type I matrix metalloproteinase (MT1-MMP) during early steps of the metastatic cascade in primary tumors remain unresolved. In an effort to determine its significance, we determined the in vivo effects of RNAi-mediated downregulation in mammary cancer cells on the migration, blood and lymphatic vessel invasion (LVI), and lymph node and lung metastasis. We also correlated the expression of cancer cell MT1-MMP with blood vessel invasion (BVI) in 102 breast cancer biopsies. MT1-MMP downregulation in cancer cells decreased lung metastasis without affecting primary tumor growth. The inhibition of lung metastasis correlated with reduced cancer cell migration and BVI. Furthermore, cancer cell-expressed MT1-MMP upregulated the expression of MT1-MMP in vascular endothelial cells, but did not affect MT1-MMP expression in lymphatic endothelial cells, LVI, or lymph node metastasis. Of clinical importance, we observed that elevated MT1-MMP expression correlated with BVI in biopsies from triplenegative breast cancers (TNBC), which have a poor prognosis and high incidence of distant metastasis, relative to other breast cancer subtypes. Together, our findings established that MT1-MMP activity in breast tumors is essential for BVI, but not LVI, and that MT1-MMP should be further explored as a predictor and therapeutic target of hematogenous metastasis in TNBC patients. Cancer Res; 71(13); 4527-38. Ó2011 AACR.

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Section: Cancer Cell Mt1-mmp Downregulation Reduces the Number Of Migmentioning

confidence: 99%

Cancer Cell–Associated MT1-MMP Promotes Blood Vessel Invasion and Distant Metastasis in Triple-Negative Mammary Tumors

Perentes

Kirkpatrick²,

Nagano³

et al. 2011

Cancer Research

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“…High MMP-14 expression is associated with early death of breast cancer patients (9) and is correlated with lymph node metastases, progression, invasion, poor clinical stage, larger tumor size, and increasing tumor stage (10,11). Taken together with the multiple lines of preclinical evidence linking MMP-14 to cancer progression, there is a strong case for targeting MMP-14 in cancer.…”

Section: Introductionmentioning

confidence: 98%

Selective Inhibition of Matrix Metalloproteinase-14 Blocks Tumor Growth, Invasion, and Angiogenesis

et al. 2009

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“…This indicated that integrin and MMPs had mutual effect .These findings suggested that α5β1-integrin plays a functional role in the invasion of studied cells, perhaps by triggering a signaling pathway controlling the activity of MMP-14 gene. Most importance was that α5β1-integrin and MMP-14 also have the common functions of activating MMP-2 [39][40][41][42] and stimulating tumor angiogenesis [25,43]. The α5β1-integrin and MMP-14 could promote each other in tumor with invasion and metastasis process and act synergistically.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological and Prognostic Significance of α5β1-integrin and MMP-14 Expressions in Colorectal Cancer

Yang¹,

Gao²,

Rao³

et al. 2013

neo

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The purpose of this study was to evaluate the association of expression level of α5β1-integrin and MMP-14 with clinicopathologic features and prognosis in colorectal cancer (CRC). The expressions of α5β1-integrin and MMP-14 in normal colorectal mucosa and CRC tissue were detected with immunohistochemistry. We estimated the five-year survival rate by the Kaplan-Meier method. The positive expressions rates of α5β1-integrin and MMP-14 in CRC tissue were 60.6% and 63.3% respectively, and there were significant differences on their positive expression rates between in CRC tissue and in normal colorectal mucosa(P<0.05). The expression rates of α5β1-integrin and MMP-14 in patients with poor histological differentiation, lymph node metastasis and high clinical staging were heightened. There was a significant difference (P<0.05) on the five-year survival rate for α5β1-integrin expression, which was 44.6% in positive groups and 75.5% in negative groups. And there was a significant difference (P<0.05) on the five-year survival rate for MMP-14 expression, which was 48.2% in positive group and 73.1% in negative group. The expression of α5β1-integrin and MMP-14 is correlated with the progression and metastasis of CRC, and α5β1-integrin and MMP-14 may be used as prognostic markers in CRC.Key words: CRC, immunohistochemistry, prognosis, survival CRC is the third most common cancer worldwide [1]. CRC is a cause of significant morbidity and cancer-related mortality in China both men and women. More than 17 million new cases of CRC were reported every year in China mainland. Despite recent treatment options and prognosis for patients with advanced CRC have improved through the development of novel drugs, progress in the treatment of CRC has been limited [2,3]. Most newly diagnosed patients will present with incurable disease, and have a median survival of less than 1 year. If metastasis has occurred, patient five-year survival rate after surgery falls dramatically from 90% to less than 10% [4]. It is, therefore, important to increase our understanding of the molecular changes leading to development, spread and metastasis of CRC and to identify potentially prognostic and predictive biomarkers for the disease.The conspicuous characteristic of malignant tumor is invasion and metastasis. To date, it is now clear that adhesive interaction play a critical role in the process of metastatic tumor dissemination [5].Cell adhesion molecules (CAMs) are involved in cell-cell and cell-extracellular matrix(ECM) binding, a highly complex process [6]. Integrins are the major adhesive molecules in cells and have been associated with metastasis of cancer cells. The integrins , a superfamily of heterodimer cell surface glycoprotein receptors composed of distinct α and β subunits [7], were originally described as cell adhesion receptors, but their functions in cell behavior including motility and invasion and their interactions with classical growth factor receptor signaling pathways have been increasingly recognized in the past few years [8]. Inte...

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The influence of MMP-14, TIMP-2 and MMP-2 expression on breast cancer prognosis

Cited by 124 publications

References 50 publications

Cancer Cell–Associated MT1-MMP Promotes Blood Vessel Invasion and Distant Metastasis in Triple-Negative Mammary Tumors

Cancer Cell–Associated MT1-MMP Promotes Blood Vessel Invasion and Distant Metastasis in Triple-Negative Mammary Tumors

Selective Inhibition of Matrix Metalloproteinase-14 Blocks Tumor Growth, Invasion, and Angiogenesis

Clinicopathological and Prognostic Significance of α5β1-integrin and MMP-14 Expressions in Colorectal Cancer

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