MMP-2 and MMP-9 Expression in Breast Cancer-Derived Human Fibroblasts is Differentially Regulated by Stromal-Epithelial Interactions

Singer, Christian F.; Kronsteiner, Nicole; Márton, Erika; Kubista, Marion; Cullen, Kevin J.; Hirtenlehner, Kora; Seifert, Michael; Kubista, E.

doi:10.1023/a:1014918512569

Cited by 136 publications

(117 citation statements)

References 36 publications

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“…The cells are able to modify the epithelial cell phenotype by direct cell-to-cell contacts, through soluble factors or by modification of ECM components. At the same time, breast cancer cells promote MMP-2 and MMP-9 expression in cancer-associated fibroblasts by stromalepithelial interactions, which form a microenvironment that contributes to the invasion and metastasis of malignant tumors (15). Premalignant mammary epithelial cells exposed to senescent human fibroblasts were reported to irreversibly become invasive and undergo a full malignant transformation (16).…”

Section: Discussionmentioning

confidence: 99%

Effect of fibroblasts on breast cancer cell mammosphere formation and regulation of stem cell-related gene expression

Zhang

Song²,

Ma³

et al. 2011

Int J Mol Med

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Section: Discussionmentioning

confidence: 99%

Effect of fibroblasts on breast cancer cell mammosphere formation and regulation of stem cell-related gene expression

Zhang

Song²,

Ma³

et al. 2011

Int J Mol Med

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“…MMP-26 did not cleave pro-MMP-2, another gelatinase, indicating that pro-MMP-9 activation by MMP-26 is highly selective. MMP-9 is a powerful enzyme, and is considered to be an important contributor to the processes of invasion, metastasis, and angiogenesis in various tumors (11)(12)(13)(14)(32)(33)(34)(35)(36).…”

Section: Reduction Of Invasiveness Of Mmp-26 Antisense Stable Transfementioning

confidence: 99%

Activation of Pro-gelatinase B by Endometase/Matrilysin-2 Promotes Invasion of Human Prostate Cancer Cells

Zhao

Xiao

Newcomer

et al. 2003

Journal of Biological Chemistry

116

140

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This work has explored a putative biochemical mechanism by which endometase/matrilysin-2/matrix metalloproteinase-26 (MMP-26) may promote human prostate cancer cell invasion. Here, we showed that the levels of MMP-26 protein in human prostate carcinomas from multiple patients were significantly higher than those in prostatitis, benign prostate hyperplasia, and normal prostate glandular tissues. The role of MMP-26 in prostate cancer progression is unknown. MMP-26 was capable of activating pro-MMP-9 by cleavage at the Ala 93 -Met 94 site of the prepro-enzyme. This activation proceeded in a time-and dose-dependent manner, facilitating the efficient cleavage of fibronectin by MMP-9. The activated MMP-9 products generated by MMP-26 appeared more stable than those cleaved by MMP-7 under the conditions tested. During the initial phases of carcinoma cell invasion, as tumor cells begin to spread and infiltrate into the surrounding normal tissues, these cells must first degrade the basement membrane and other elements of the extracellular matrix (ECM), 1 including type IV collagen, laminin, and fibronectin (FN) (1). Multiple protease families, including the matrix metalloproteinases (MMPs), serine proteases, and cysteine proteases, are suspected of contributing to the invasive and metastatic abilities of a variety of malignant tumors (2-5), but the specific biochemical mechanisms that facilitate these invasive behaviors remain elusive.More than 23 human MMPs, and numerous homologues from other species, have been reported (5), and matrix metalloproteinase-26 (MMP-26)/endometase/matrilysin-2 is a novel member of this enzyme family that was recently cloned and characterized by our group (6) and others (7-9). MMP-26 mRNA is primarily expressed in epithelial cancers, such as lung, breast, endometrial, and prostate carcinomas, in their corresponding cell lines (6 -9), and in a very limited number of normal adult tissues, such as the uterus (6, 8), placenta (7,8), and kidney (9). Recently, we have found that the levels of MMP-26 gene and protein expression are higher in a malignant choriocarcinoma cell line (JEG-3) than in normal human cytotrophoblast cells (10). Our preliminary studies indicate that expression of MMP-26 may be correlated with the malignant transformation of human prostate and breast epithelial cells. The specific expression of MMP-26 in malignant tumors and the proteolytic activity of this enzyme against multiple components of the ECM, including fibronectin, type IV collagen, vitronectin, gelatins, and fibrinogen, as well as non-ECM proteins such as insulin-like growth factor-binding protein 1 and ␣1-protease inhibitor (6 -9), indicate that MMP-26 may possess an important function in tumor progression.Another member of the MMP family considered to be an important contributor to the processes of invasion, metastasis, and angiogenesis exhibited by tumor cells is gelatinase B (MMP-9) (11-14). Uría and López-Otín (8) have demonstrated that MMP-26 is able to cleave MMP-9, and here we examine the possibility that MMP...

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“…[32][33][34][35] In particular, MMP-2 is mainly produced by stromal fibroblasts of breast tumors. [35][36][37] It has been demonstrated that malignant breast tumor cells can enhance MMP-2 production in surrounding fibroblasts; cancer cells can subsequently use MMP-2 produced by the fibroblasts to facilitate their egress from tumor mass and entry into new sites. 38 Breast tumor cells may not be the only target of ethanol action; ethanol may affect stromal cells and disrupt the tumor-stroma interaction.…”

mentioning

confidence: 99%

“…30 Interestingly, in most cases the two MMPs are not produced by malignant epithelium itself, but rather by surrounding tumor stroma. [32][33][34][35] In particular, MMP-2 is mainly produced by stromal fibroblasts of breast tumors. [35][36][37] It has been demonstrated that malignant breast tumor cells can enhance MMP-2 production in surrounding fibroblasts; cancer cells can subsequently use MMP-2 produced by the fibroblasts to facilitate their egress from tumor mass and entry into new sites.…”

mentioning

confidence: 99%

Ethanol‐induced in vitro invasion of breast cancer cells: The contribution of MMP‐2 by fibroblasts

Aye

Lin

et al. 2004

Intl Journal of Cancer

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Ethanol is a tumor promoter and may promote metastasis of breast cancer. However, the underlying cellular/molecular mechanisms remain unknown. Overexpression and high activity of matrix metalloproteinase-2 (MMP-2) are frequently associated with metastatic breast cancers and serve as a prognostic indicator of clinical outcome. MMP-2 is predominantly expressed in stromal fibroblasts and plays a pivotal role in regulating the invasive behavior of breast tumor cells. We hypothesized that ethanol may enhance the invasion of breast tumor cells by modulating the activity of fibroblastic MMP-2. With in vitro models (HS68 and CCD1056SK human fibroblasts), we showed that ethanol at physiologically relevant concentrations (50 -200 mg/dl) activated MMP-2; conversely, at a higher concentration (400 mg/dl), it inhibited the MMP-2 activity. Consistently, conditioned medium collected from ethanol ( Key words: alcohol; ErbB; metastasis; proteinases; signal transductionBreast cancer is a leading cause of morbidity and mortality in women. 1 The endogenous and environmental factors that contribute to its etiology remain elusive. Despite being responsive to hormonal manipulation and chemotherapy, relapse after treatment is common, particularly in patients presenting with metastatic disease. 2 The metastatic process involves the degradation of different macromolecular components of the extracellular matrix (ECM) and basement membranes and is regulated by intrinsic properties of the tumor cells as well as microenvironmental factors. Alcohol is a tumor promoter; there is a positive correlation between alcohol intake and the risk of several human cancers, including mouth/oropharyngeal cancer, oesophageal cancer, liver cancer and breast cancer. [3][4][5][6][7][8][9][10][11] Epidemiologic studies indicate that alcohol consumption is associated with advanced and invasive breast tumors, [12][13][14] suggesting that alcohol may enhance tumor development and metastasis. These epidemiologic results are supported by experimental studies using animal models and cell culture systems, which show that ethanol promotes mammary tumorigenesis and stimulates proliferation as well as invasion of breast cancer cells. [15][16][17][18][19][20][21] The molecular mechanisms underlying ethanol action, however, remain to be determined.Abnormal communication between the mammary epithelium and stromal cells promotes tumorigenesis and development of breast carcinomas. 22 Cancer-stroma interaction is mediated at least in part through the matrix metalloproteinases (MMPs). MMPs are a family of zinc-dependent endopeptidases that collectively are capable of degrading all components of the ECM. MMPs have been implicated in normal matrix remodeling events such as development of the mammary gland 23 and in pathologic conditions, including tumor invasion and metastasis. 24 Coupled with their function in metastasis, the MMPs also have a role in carcinogenesis. 25,26 High levels of MMP-2 and MMP-9 have been found to correlate with enhanced metastasis and poor prognosis in ...

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MMP-2 and MMP-9 Expression in Breast Cancer-Derived Human Fibroblasts is Differentially Regulated by Stromal-Epithelial Interactions

Cited by 136 publications

References 36 publications

Effect of fibroblasts on breast cancer cell mammosphere formation and regulation of stem cell-related gene expression

Effect of fibroblasts on breast cancer cell mammosphere formation and regulation of stem cell-related gene expression

Activation of Pro-gelatinase B by Endometase/Matrilysin-2 Promotes Invasion of Human Prostate Cancer Cells

Ethanol‐induced in vitro invasion of breast cancer cells: The contribution of MMP‐2 by fibroblasts

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