SciMedWeb® - MATRIX METALLOPROTEINASE-9 (MMP9)

Cell lines:
- MMP-2 activation was induced by collaggen I culture only in aggressive, highly invasive estrogen receptor-negative, vimentin-positive human breast cancer cell lines (Hs578T, MDA-MB-436, BT549, MDA-MB-231, MDA-MB-435, MCF-7 ADR) and was independent of MMP-2 production. MMP-2 activation was detected in cells cultured on collagen I gels but not in those cultured on gelatin gels, Matrigel, or thin layers of collagen I or IV, gelatin, or fibronectin. Collagen-induced activation was specific for the enzyme species MMP-2, since MMP-9 was not activatable under similar conditions (Azzam H.S. et al., 1993).

- Incubation of c-erbb2 (HER-2/neu)-overrexpressing SK-BR-3 breast cancer cells (BCC) with heregulin inhibited anchorage-independent growth while enhancing tyrosine phosphorylation of c-erbB2. Heregulin treatment also increased adhesion of SK-BR-3 cells to plastic and increased invasiveness of tumor cells into Matrigel membranes while increasing expression of the CD44 and CD54 (ICAM-1) adhesion molecules. Tumor cell invasion of Matrigel membranes was partially blocked by either anti-CD44 or anti-CD54 antibodies, indicating a role for these adhesion molecules in the invasion process. Compatible with the increased invasiveness, heregulin increased expression of MMP-9 (Xu F.J. et al., 1997).

- Genistein is a natural flavone compounnd found in soy. Genistein was found to exert pronounced antiproliferative effects on both estrogen receptor-positive and -negative human BCC through G₂-M arrest, induction of p21WAF1/CIP1 (gene CDKN1A) expression, and apoptosis. Genistein inhibited invasion in vitro of MCF-7 and MDA-MB-231 BCC. This inhibition was characterized by down-regulation of MMP (matrix metalloproteinase)-9 and up-regulation of tissue inhibitor of metalloproteinase-1 (TIMP-1), the former of which was transcriptionally regulated at activation protein-1 sites in the MMP-9 promoter. Genistein's in vitro effects on MMP-9 and TIMP-1 were also demonstrated in in vivo studies in nude mouse xenografts of MDA-MB-231 and MCF-7 BCC. In these xenograft studies, genistein inhibited tumor growth, stimulated apoptosis, and upregulated p21WAF1/CIP1 expression. In the MDA-MB-231 xenograft, genistein also inhibited angiogenesis by decreasing vessel density and decreasing the levels of vascular endothelial growth factor and transforming growth factor-beta1 (Shao Z.M. et al., 1998).

- The shedding of membrane vesicles fromm the cell surface is a vital process considered to be involved in cell-cell and cell-matrix interactions and in tumor progression. By immunoelectron microscopic analysis of surface replicas of 8701-BC human breast carcinoma cells, membrane vesicles shed from plasma membranes were found to contain densely clustered MMP-9, beta₁ integrins, and human lymphocyte antigen class I molecules. Vesicle shedding occurred preferentially at the edge or along narrow protrusions of the cell. Specific accumulation of proMMP-9 and active forms of MMP-9 in shed vesicles was also demonstrated by gelatin zymography. In addition, Western blotting analysis showed the presence of a large amount of proMMP-9/TIMP-1 complex (Dolo V. et al., 1998).

- EGF was found to stimulate the motile and invasive activities specifically in the ErbB-2-overexpressing SK-BR-3 cells. Expression of extracellular matrix-degrading proteases including type I collagenase/MMP-1, 92 kDa type IV collagenase/MMP-9, uPA and uPA receptor were induced. EGF also transiently stimulated expression of the transcription factors Ets-1 and Ets-2. Reporter transfection assays revealed the activation of uPA and MMP-9 collagenase promoters by EGF and the requirement of each of the composite Ets and AP-1 transcription factor binding sites for an EGF response (Watabe T. et al., 1998).

- In SK-BR-3 BCC, binding of epidermal ggrowth factor (EGF) and amphiregulin to EGF receptor (EGFR) results in EGFR autophosphorylation, increased cell proliferation and induction of MMP-9. Inhibitors of mitogen-activated protein kinase (MAPK) or MAPK kinase (MAPKK) blocked EGF-induced cell proliferation and MMP-9 induction and invasion of BCC through Matrigel. These inhibitors also blocked the induction of MMP-9 by the phorbol ester TPA in MDA-MB-231 BCC (Reddy K.B. et al., 1999).

- TGF-beta1 is found in high amounts in bone. It was found to induce MMP9 activity and protein expression in the bone-metastatic MDA-MB-231 BCC (Duivenvoorden W.C. et al., 1999).

- Protein kinase C activation was found to dramatically increase the expression and secretion of MMP9 by MCF-7 BCC, though all of the enzyme secreted was in the latent form (Johnson M.D. et al., 1999).

- To examine MMP-9 activation in a celluular setting, cultures of human tumor cells that were induced to produce MMP-9 over a 200-fold concentration range (0.03 to 8.1 nM) were used. Plasmin, generated by the endogenous plasminogen activator (uPA), is not an efficient activator of proMMP-9. Plasmin, however, is very efficient at generating active MMP-3 from exogenously added proMMP-3. The activated MMP-3, when its concentration exceeds that to TIMP, becomes a potent activator of proMMP-9. Addition to the cultures of already-activated MMP-3 relinquishes the requirement for plasminogen and proMMP-3 additions and results in direct activation of the endogenous proMMP-9. The activated MMP-9 enhances the invasive phenotype of the cultured cells as their ability to transverse basement membrane is significantly increased following zymogen activation (Hahn-Dantona E. et al., 1999).

- Overexpression of cJun in MCF-7 BCC caaused significant alterations in the composition of AP-1, decreased junB and increased fra-1 expression and resulted in an increased biologic aggressiveness. MCF7Jun cells exhibited increased cellular motility, increased expression of MMP-9, increased in vitro chemoinvasion and tumor formation in nude mice in the absence of exogenous estrogens. Furthermore, MCF7Jun cells were unresponsive to the growth stimulating effects of estrogen and growth inhibitory effects of tamoxifen. Analysis of the estrogen receptor (ER) expression and activity showed that the MCF7Jun cells had no detectable ER. MCF-7 cells overexpressing mutant forms of cJun were responsive to the growth stimulatory effects of estrogen indicating that full-length cJun is required to acquire the estrogen-independent phenotype in breast cancer cells (Smith L.M. et al., 1999).

- Data suggest that IGF-I-induced MCF-7 BCC migration through vitronectin filters is mediated by the MMP-9 activity on the cell surface and by alpha_Vbeta₅ integrin (Mira E. et al., 1999).

- Bcl-2-mediated regulation of NF-kappaBB-transcription-factor activity may lead to the up-regulation of MMP9 transcription in MCF-7/Adr BCC (Ricca A. et al., 2000).

- Analysis of MMP expression by RT-PCR sshowed expression of MMP-1, MMP-3, and MMP-13 in highly invasive MDA-MB-231 BCC, but not in slightly invasive MCF-7, T-47D, and BT-20 cell lines. The extracellular secretion of MMP-1 and MMP-3 by MDA-MB 231 cells could be also shown by ELISA. TIMP-1 and TIMP-2 mRNAs were found in all cell lines, however, the extracellular secretion of both TIMPs was much higher in MDA-MB-231 cells than in the other cell lines. When the cells were cultured on Matrigel matrix, MMP-9 expression was induced in MDA-MB-231 cells only, as assessed by RT-PCR and zymography experiments. The invasive potential of MDA-MB-231 cells evaluated in vitro through Matrigel was significantly inhibited by the MMP inhibitor BB-2516 (Balduyck M et al., 2000).

- N-cadherin (CDH2), is expressed in higghly invasive tumor cell lines that lack E-cadherin (CDH1) expression. To determine whether N-cadherin promotes invasion and metastasis, a weakly metastatic and E-cadherin-expressing breast cancer cell line, MCF-7, was transfected with N-cadherin and the effects on cell migration, invasion, and metastasis were analyzed. Transfected cells expressed both E- and N-cadherin and exhibited homotypic cell adhesion from both molecules. In vitro, N-cadherin-expressing cells migrated more efficiently, showed an increased invasion of Matrigel, and adhered more efficiently to monolayers of endothelial cells. All cells produced low levels of the matrix metalloproteinase MMP-9, which was dramatically upregulated by treatment with FGF-2 only in N-cadherin-expressing cells. Migration and invasion of Matrigel were also greatly enhanced by this treatment. When injected into the mammary fat pad of nude mice, N-cadherin-expressing cells, but not control MCF-7 cells, metastasized widely to the liver, pancreas, salivary gland, omentum, lung, lymph nodes, and lumbar spinal muscle. The expression of both E- and N-cadherin was maintained both in the primary tumors and metastatic lesions. These results demonstrate that N-cadherin promotes motility, invasion, and metastasis even in the presence of the normally suppressive E-cadherin (Hazan R.B. et al., 2000).

- The alpha₃beta₁ integrin is elevated in several types of metastatic tumor and has been associated with increased migration and invasion. Treatment of MDA-MB-231 cells with a function-blocking anti-alpha₃ antibody strongly inhibited migration and invasion. This correlated with a marked reduction in MMP-9 activity (Morini M. et al., 2000).

- The hyaluronan receptor CD44 provides a cell surface docking receptor for proteolytically active MMP-9 (Yu Q. and Stamenkovic I., 2000).

- The Ets-1 transcription factor transacctivates several genes encoding matrix-degrading proteases and is thought to be involved in both tumour vascularization and invasion. During breast cancer formation, as shown by in situ hybridization and immunohistochemistry, the Ets-1, MMP1, and MMP9 genes were first expressed within both endothelial cells and stromal fibroblasts during the onset of stroma generation around intraductal and intralobular in situ carcinomas and they were significantly up-regulated in the stroma of invasive ductal and lobular cancers (Behrens P. et al., 2001).

Tumors:
- In situ hybridization studies have shoown that the expression of MMP-2 mRNA is mostly localized to tumor fibroblasts, while MMP-9 mRNA is expressed by epithelial cells and macrophages (Polette M. et al., 1993).

- Immunohistological staining of MMP-2 aand MMP-9, basal lamina collagen IV and TIMP-2 were performed on frozen sections of 83 invasive breast carcinomas. MMP-2 and MMP-9 were associated with neoplastic cell plasma membrane in 72% of cases and exhibited inter-tumoral variability of staining intensity. MMP-2 and MMP-9 staining was not correlated with presence of metastases at time of diagnosis or with disease outcome. TIMP-2 was detected in the peri-tumoral stroma and was present in 87% of cases. Residual benign breast tissue was negative for TIMP-2 staining. Neoplasms with diffuse TIMP-2 staining (24%) recurred significantly more frequently (75% recurred) than cases with focal (42% recurred) or absent (27% recurred) TIMP-2. Presence of collagen IV was negatively correlated with gelatinase staining (Visscher D.W. et al., 1994).

- The presence of mRNAs for MMP-2 and -99, alpha 1 (IV) chain of Type IV collagen, and laminin B1 chain was investigated by in situ hybridization in 20 breast carcinomas of various histological types. The mRNA signals for MMP-2, Type IV collagen, and laminin were much more abundant in stromal fibroblasts and endothelial cells than in carcinoma cells. The signal for MMP-9 mRNA was strong in carcinoma cells and considerably weaker in stromal fibroblasts and endothelial cells. Labeling for MMP-2 and -9 mRNA was also found in benign fibroadenomas and for MMP-9 in non-neoplastic ducts and acini (Soini Y. et al., 1994).

- In a series of 55 breast tumours, leveels of both MMP8 and MMP9 were significantly related to concentration of TIMP-1 (for MMP8, P=0.0035; for MMP9, P=0.0021). Levels of MMP8, MMP9, and TIMP-1 showed no significant correlation with either tumor size or axillary node metastasis (Duffy M.J. et al., 1995).

- It has been suggested that MMP9 in humman breast cancer is located in tumor-infiltrating stromal cells, including neutrophils, macrophages, and vascular pericytes, and that the latter two cell types also produce this metalloprotease (Nielsen B.S. et al., 1997).

- The activity of MMP-9 from 28 normal, 12 benign and 126 breast cancer tissues was measured using gelatin zymography with an image analysis system. ProMMP-9 was expressed in 17.5% of the cancer patients compared to 2.5% in 40 non-cancerous tissues (p = 0.014). The mature form of MMP-9 (82 kD) was expressed only in T2-T4 stages. During the early phase of breast cancer (DCIS and T1 stage) progression, only production of proMMP-9 increased. However, as the cancer grew or invaded skin (T2-T4), or with lymphovascular permeation, both production and activation of MMP-9 increased (Rha S.Y. et al., 1999).

- Exposure of SKBR-3 BCC to epidermal grrowth factor (EGF) or amphiregulin (AR) induced expression of MMP9 but had no effect on MMP2 secretion. In contrast to EGF and AR, heregulin had no effect on gelatinase induction. None of the EGF polypeptides had any effect on gelatinase induction in MCF-7 non-metastatic breast cancer cells (Kondapaka S.B. et al., 1997).

- In a series of 34 breast cancer patiennts, no correlation was found between high levels of TIMP-1 mRNA and MMP-2 and MMP-9 mRNA levels (Ree A.H. et al., 1997).

- The association among matrix metalloprroteinases (gelatinases A/MMP-2 and B/MMP-9, stromelysin-3/MMP-11 and matrilysin/MMP-7) mRNAs expressed in primary breast carcinomas was investigated and standard prognostic parameters and clinical outcome. mRNA levels were determined by Northern analysis in samples of 81 breast cancer patients (median follow-up, 40 months) and 27 samples of uninvolved adjacent breast tissue. Proteases were expressed by the majority of the tumors and normal breast tissues examined. MMP-11, MMP-2 and MMP-7 mRNAs were more often expressed at high levels in carcinomatous than in normal breast tissues. Differences in the distribution of MMP-9 mRNA were not found. However, paired normal tissues generally produced weaker signals when compared to matched tumor samples. Univariate analysis showed no significant association of MMP-2 and MMP-7 mRNAs with the classical prognostic markers (age, menopausal status, stage, size, nodal status, vascular infiltrate, necrosis, steroid receptors, metastasis and survival). Overexpression of MMP-11 was more frequently found in tumors of post-menopausal women (P < 0.022). Elevated expression of MMP-9 mRNA was associated with the presence of vascular infiltrate (P < 0.026), necrosis (P < 0.039), PR negative tumors (P < 0.014) and inversely correlated to the number of survivors (P < 0.021). Multivariate analysis including 68 patients for whom all information was available indicated that neither stromelysin correlated significantly with pathological, clinical or biochemical features. High levels of MMP-2 and -9 mRNAs were inversely associated with the number of survivors (Pacheco M.M. et al., 1998).

- By substrate zymography, MMP9 was meassured in paired tumour and normal tissue samples from 43 breast cancer patients. Latent MMP9 was found in 100% breast tumour samples and 93% normal breast, but the amount of the enzyme was significantly greater in tumour tissue than than in the corresponding normal tissue samples. Active MMP9 was expressed in 78% breast tumours and only 7% normal breast samples (Garbett E.A. et al., 1999).

- In primary breast cancers, TIMP-1 leveels were found to be weakly but significantly correlated with those for MMP1, proMMP2, active MMP2, MMP3 and proMMP9 (McCarthy K. et al., 1999).

- Material from 65 cases of invasive ducctal breast cancer was analyzed by immunohistochemistry for the localization of MMP-2, -3 and -9 and by the non-radioactive in-situ hybridization technique for the localization of the MMP-3-mRNA. A distinct positive immunoreaction for MMP-2, -3 and -9 was observed over both invasive, as well as non-invasive tumor cells, without apparent differences in the staining intensity. There was a significant staining of tumor cell complexes undergoing lymphangiotic dissemination. In addition to this tumor cell staining pattern, a positive immunoreaction, although to reduced proportion, was observed over peritumoral fibroblastic and endothelial stroma cells. Normal breast tissue also revealed a positive immunostaining of epithelial and stromal cells. By in-situ hybridization, mRNA expression for MMP-3 was observed both in tumor and stroma cells, comparable to the protein data. Normal breast epithelia reacted weakly positive for MMP-3-mRNA (Lebeau A. et al., 1999).

- MMP-2, MT1-MMP (MMP14), and MMP-9 exprression was studied by immunohistochemistry in a series of 79 infiltrating ductal carcinomas (IDCs), 8 tubular carcinomas, and 27 infiltrating lobular carcinomas (ILCs). MMP-2 and MT1-MMP were expressed in more than 90 per cent of all carcinomas, with predominantly stromal and tumour cell cytoplasmic staining. However, reactivity localized on tumour cell membranes was recorded for MMP-2 in 34 per cent of cases with a monoclonal antibody and 55 per cent of cases with a polyclonal antibody, and for MT1-MMP in 68 per cent of tumours. MMP-9 was expressed by 68 per cent of carcinomas, either in the stromal compartment or by tumour cells. There was a highly significant correlation between the expression pattern of MMP-9 and tumour type, with ILCs displaying greater frequency and more homogeneous cytoplasmic staining than IDCs (p=0.0004) (Jones J.L. et al., 1999).

- In normal as well as in malignant tisssue, both MMP-2 and MMP-9 occur in multiple forms such as inactive precursors, active enzymes and enzyme-inhibitor complexes. The levels of active MMP2, total (active and activatable) MMP2 and total MMP9 were found to be significantly higher in breast carcinomas than in fibroadenomas. In addition, active MMP2 and MMP9 were detected more frequently in malignant than in benign breast carcinoma (Hanemaaijer R. et al., 2000).

- Thirty one specimens of bone metastasiis from breast carcinoma were stained for MMP1, 2, 9, 14 (MT1-MMP) and TIMP1, and 2 and compared with staining in normal breast tissue, primary breast carcinoma and normal bone. No major differences in the MMP/TIMP staining of tumor cells and fibroblasts were observed between bone metastasis and primary tumor. The number and activity of osteoclasts and osteoblasts was increased dramatically in bone metastases, their MMP/TIMP profiles, however, were not different from normal bone, suggesting that the mechanism of bone degradation by osteoclasts is not different from normal bone remodelling (Lhotak S. et al., 2000).

- By gelatin zymography, MMP activity waas evaluated in the euglobulin plasma fraction of 82 healthy controls, 66 patients with benign diseases and 149 patients with breast, lung, colon or brain cancer. The euglobulin fractions assayed showed 4 gelatinolytic bands of 62, 92, 120 and 200 kDa. The median (Md) value for 92 kDa-MMP activity was significantly increased in breast (Md 1.34 arbitrary units [AU]/ml plasma, range 0.0-7.2) and lung cancer patients (Md 1.43 AU/ml, range 0.0-3.6) compared with the controls (Md 0.48 AU/ml, range 0.0-1.8). Multivariate analysis indicated that plasma MMP-9 activity was not predicted by the known clinicopathological parameters such as age, stage, tumor size, number of positive lymph nodes, histologic grade, histologic type, nuclear grade or mitotic index (Farias E. et al., 2000).

- Using Northern blot analysis, the co-eexpression of the matrix metalloprotease MMP-9, plasminogen activator urokinase type (uPA) and its receptor (uPAR) mRNAs was determined in 81 biopsies of breast carcinomas (median follow-up time of patients: 4 years). Individual mRNA levels of either uPA or uPAR showed parallel variations with MMP-9 mRNA, suggesting a coordinate transcription of these markers. When median values were used as cutoff points to discriminate between high and low factor expression, no association was found with patient outcome and MMP-9 or uPA mRNA distribution. However, increased uPAR mRNA levels were associated with poor prognosis (p = 0.01). The combination of MMP-9 and uPAR mRNA measurements has not enhanced prognostic information compared to information supplied by the receptor alone (p = 0.01). The combination of MMP-9 and high levels of uPA mRNA led to a significant association with poor outcome (p = 0.03). Multivariate analysis supported the notion that increased uPAR mRNA production in primary breast cancer may be a predictor of overall survival (Pacheco M.M. et al., 2001).

- The prognostic value of MMP-9 was evalluated by immunoperoxidase staining in a series of 210 breast cancer tissues. The results were quantitated using the HSCORE system, which consider both staining intensity and the percentage of cells stained at given intensities. MMP-9 staining was observed primarily in cancer cells, and to a lesser degree in surrounding stromal cells. MMP-9 expression was not detected in normal breast tissue. Levels of MMP-9 expression below the cut-off point were more frequently observed in larger (P = 0.014), invasive ductal histologic (P = 0.037), progesterone receptor (PR)-negative and PR-strong positive tumours (P< 0.001), as well as samples belonging to patients with stage III-IV disease (P = 0.009) and age 45-55 years (P = 0.011). In univariate analysis, node-negative breast cancer patients with tumors positive for MMP-9 had a considerable reduction in risk for relapse (RR = 0.45;P = 0.039) or death (RR = 0.32;P = 0.009). Multivariate analysis indicated that MMP-9 status was an independent favourable predictor of overall survival (RR = 0.47;P = 0.034) in node-negative but not in node-positive patients (Scorilas A. et al., 2001).

Azzam H.S. et al. (1993) Association of MMP-2 activation potential with metastatic progression in human breast cancer cell lines independent of MMP-2 production. J. Natl. Cancer Inst. 85, 1758-1764. (PubMed)
Balduyck M. et al. (2000) Specific expression of matrix metalloproteinases 1, 3, 9 and 13 associated with invasiveness of breast cancer cells in vitro. Clin. Exp. Metastasis 18, 171-178. (PubMed)
Behrens P. et al. (2001) The Ets-1 transcription factor is up-regulated together with MMP 1 and MMP 9 in the stroma of pre-invasive breast cancer. J. Pathol. 194, 43-50. (PubMed)
Devarajan P. et al. (1992) Structure and expression of neutrophil gelatinase cDNA. Identity with type IV collagenase from HT1080 cells. J. Biol. Chem. 267, 25228-25232. (PubMed)
Dolo V. et al. (1998) Selective localization of matrix metalloproteinase 9, beta1 integrins, and human lymphocyte antigen class I molecules on membrane vesicles shed by 8701-BC breast carcinoma cells. Cancer Res. 58, 4468-4474. (PubMed)
Duivenvoorden W.C. et al. (1999) Transforming growth factor beta1 acts as an inducer of matrix metalloproteinase expression and activity in human bone-metastasizing cancer cells. Clin. Exp. Metastasis 17, 27-34. (PubMed)
Duffy M.J. et al. (1995) Assay of matrix metalloproteases types 8 and 9 by ELISA in human breast cancer. Br. J. Cancer 71, 1025-1028. (PubMed)
Farias E. et al. (2000) Plasma metalloproteinase activity is enhanced in the euglobulin fraction of breast and lung cancer patients. Int. J. Cancer 89, 389-394. (PubMed)
Garbett E.A. et al. (1999) Proteolysis in human breast and colorectal cancer. Br. J. Cancer 81, 287-293. (PubMed)
Hahn-Dantona E. et al. (1999) Activation of proMMP-9 by a plasmin/MMP-3 cascade in a tumor cell model. Regulation by tissue inhibitors of metalloproteinases. Ann. N.Y. Acad. Sci. 878, 372-387. (PubMed)
Hanemaaijer R. et al. (2000) Increased gelatinase-A and gelatinase-B activities in malignant vs. benign breast tumors. Int. J. Cancer 86, 204-207. (PubMed)
Hazan R.B. et al. (2000) Exogenous expression of N-cadherin in breast cancer cells induces cell migration, invasion, and metastasis. J. Cell Biol. 148, 779-790. (PubMed)
Huhtala P. et al. (1991) Complete structure of the human gene for 92-kDa type IV collagenase: divergent regulation of expression for the 92- and 72-kilodalton enzyme genes in HT-1080 cells. J. Biol. Chem. 266, 16485-16490.(PubMed)
Johnson M.D. et al. (1999) Regulation of motility and protease expression in PKC-mediated induction of MCF-7 breast cancer cell invasiveness. Exp. Cell Res. 247, 105-113. (PubMed)
Jones J.L. et al. (1999) Expression of MMP-2 and MMP-9, their inhibitors, and the activator MT1-MMP in primary breast carcinomas. J. Pathol. 189, 161-168. (PubMed)
Kondapaka S.B. et al. (1997) Epidermal growth factor and amphiregulin up-regulate matrix metalloproteinase-9 (MMP-9) in human breast cancer cells. Int. J. Cancer 70, 722-726. (PubMed)
Lebeau A. et al. (1999) Tissue distribution of major matrix metalloproteinases and their transcripts in human breast carcinomas. Anticancer Res. 19, 4257-4264. (PubMed)
Lhotak S. et al. (2000) Immunolocalization of matrix metalloproteinases and their inhibitors in clinical specimens of bone metastasis from breast carcinoma. Clin. Exp. Metastasis 18, 463-470. (PubMed)
McCarthy K. et al. (1999) High levels of tissue inhibitor of metalloproteinase-1 predict poor outcome in patients with breast cancer. Int. J. Cancer 84, 44-48. (PubMed)
Mira E. et al. (1999) Insulin-like growth factor I-triggered cell migration and invasion are mediated by matrix metalloproteinase-9. Endocrinology 140, 1657-1664. (PubMed)
Morini M. et al. (2000) The alpha 3 beta 1 integrin is associated with mammary carcinoma cell metastasis, invasion, and gelatinase B (MMP-9) activity. Int. J. Cancer 87, 336-342. (PubMed)
Nielsen B.S. et al. (1997) Expression of matrix metalloprotease-9 in vascular pericytes in human breast cancer. Lab. Invest. 77, 345-355. (PubMed)
Pacheco M.M. et al. (1998) Expression of gelatinases A and B, stromelysin-3 and matrilysin genes in breast carcinomas: clinico-pathological correlations. Clin. Exp. Metastasis 16, 577-585. (PubMed)
Pacheco M.M. et al. (2001) Prognostic significance of the combined expression of matrix metalloproteinase-9, urokinase type plasminogen activator and its receptor in breast cancer as measured by Northern blot analysis. Int. J. Biol. Markers 16, 62-68. (PubMed)
Polette M. et al. (1993) detection and localization of mRNAs encoding matrix metalloproteinases and their tissue inhibitor in human breast pathology. Invasion Metastasis 13, 31-37. (PubMed)
Reddy K.B. et al. (1999) Mitogen-activated protein kinase (MAPK) regulates the expression of progelatinase B (MMP-9) in breast epithelial cells. Int. J. Cancer 82, 268-273. (PubMed)
Ree A.H. et al. (1997) High levels of messenger RNAs for tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in primary breast carcinomas are associated with development of distant metastases. Clin. Cancer Res. 3, 1623-1628. (PubMed)
Rha S.Y. et al. (1999) Sequential production and activation of matrix-metalloproteinase-9 (MMP-9) with breast cancer progression. Breast Cancer Res. Treat. 43, 175-181. (PubMed)
Ricca A. et al. (2000) bcl-2 over-expression enhances NF-kappaB activity and induces mmp-9 transcription in human MCF7(ADR) breast-cancer cells. Int. J. Cancer 86, 188-196. (PubMed)
Scorilas A. et al. (2001) Overexpression of matrix-metalloproteinase-9 in human breast cancer: a potential favourable indicator in node-negative patients. Br. J. Cancer 84, 1488-1496. (PubMed)
Shao Z.M. et al. (1998) Genistein exerts multiple suppressive effects on human breast carcinoma cells. Cancer Res. 58, 4851-4857. (PubMed)
Smith L.M. et al. (1999) cJun overexpression in MCF-7 breast cancer cells produces a tumorigenic, invasive and hormone resistant phenotype. Oncogene 18, 6063-6070. (PubMed)
Soini Y. et al. (1994) 72 KD and 92 KD type IV collagenase, type IV collagen, and laminin mRNAs in breast cancer: a study by in situ hybridization. J. Histochem. Cytochem. 42, 945-951. (PubMed)
St Jean P.L. et al. (1995) Characterization of a dinucleotide repeat in the 92 kDa type IV collagenase gene (CLG4B), localization of CLG4B to chromosome 20 and the role of CLG4B in aortic aneurysmal disease. Ann. Hum. Genet. 59, 17-24. (PubMed)
Visscher D.W. et al. (1994) Enhanced expression of tissue inhibitor of metalloproteinase-2 (TIMP-2) in the stroma of breast carcinomas correlates with tumor recurrence. Int. J. Cancer 59, 339-344. (PubMed)
Watabe T. et al. (1998) The Ets-1 and Ets-2 transcription factors activate the promoters for invasion-associated urokinase and collagenase genes in response to epidermal growth factor. Int. J. Cancer 77, 128-137. (PubMed)
Xu F.J. et al. (1997) Heregulin and agonistic anti-p185(c-erbB2) antibodies inhibit proliferation but increase invasiveness of breast cancer cells that overexpress p185(c-erbB2): increased invasiveness may contribute to poor prognosis. Clin. Cancer Res. 3, 1629-1634. (PubMed)
Yu Q. and Stamenkovic I. (2000) Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes Dev. 14, 163-176. (PubMed)

Markers in breast cancer

Matrix metalloproteinase-9
(MMP9, MMP-9)

Other name(s)

Molecular biology

Breast cancer

References

See also

Latest modification of this page

Made in WALLONIA / EUREGIO MAAS-RHINE - Fait en WALLONIE / EUREGIO MEUSE-RHIN - Marc Lacroix & SciMedWeb® 1997-2002