Matrix metalloproteinase-2
(MMP2, MMP-2)

Gelatinase A
72-kD gelatinase
Type IV collagenase
EC Number: EC3.4.24.24

Gene: MMP2 maps to 16q13. The gene is 17 kb long with 13 exons (as also observed in MMP9) varying in size from 110 to 901 bp and 12 introns ranging from 175 to 4,350 bp. Alignment of introns showed that introns 1 to 4 and 8 to 12 of the type IV collagenase gene coincide with intron locations in the MMP1 and MMP3 genes, indicating a close structural relationship of these metalloproteinase genes. Analysis of the 0.4-kb 5'-flanking region of the gene showed that, in contrast to the genes of interstitial collagenease and stromelysin, there is no TATA box or 12-O-tetradecanoylphorbol-13-acetate-responsive element present in the promoter region, whereas there are two GC boxes. There is no CAAT box, but a potential binding site (CCCCAGGC) for the transcription factor AP-2 is located in the first exon (Huhtala et al., 1990).
mRNA: size: ~3.1 kb.
Protein: MMP2 is secreted as a pro-enzyme, whose cleavage leads to the production of a soluble active form that is further trapped by receptors present at the surface of cancer cells (Brooks P. et al., 1996). MMP2 activation from the pro- to the mature form is a complex mechanism involving the membrane-type MMPs (MT-MMPs). MT1-MMP (MMP14) is the most potent activator of MMP2. The extracellular activity of MMPs is inhibited when they form complexes with specific inhibitors, such as TIMP1 and TIMP2.
See also: structural and functional characteristics of MMPs

MMP2 plays a crucial role in carcinomas since its specific substrate is type IV collagen, a major component of the basement membrane that is highly modified during the invasive steps of the disease.

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).

- Observations suggest that MCF-7 breastt cancer cells (BCC) in culture produce both soluble and membrane-bound factor(s) which stimulate the production of pro-MMPs (including MMP2) and TIMP-1 in neighbouring stromal cells, but the factor(s) released into the medium and that associated with cell membranes are probably different. Such communication between the normal and malignant cell types may, in part, assist the cancer cells to invade and metastasise (Ito A. et al., 1995).

- 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 BCC (Kondapaka S.B. et al., 1997).

- Osteonectin was found to induce MMP2 aactivation in two invasive breast cancer cell (BCC) lines (MDA-MB-231 and BT-549) but not in a noninvasive counterpart (MCF-7), which lacks MMP14 (MT1-MMP) -an important determinant of MMP2 activation. The activity of OSN was restricted to a peptide corresponding to the NH₂-terminal region of the protein (Gilles C. et al., 1998).

- Data indicate that alpha₃beeta₁-tetraspanin protein complexes may control invasive migration of MDA-MB-231 BCC by using at least two PI3K-dependent signaling mechanisms: through rearrangement of the actin cytoskeleton and by modulating the MMP-2 production (Sugiura T. and Berditchevski F., 1999).

- MMP2 could be a p53 target and subjectt to p53 upregulation. However, wild-type p53 induced by gamma-irradiation did not cause a subsequent increase of MMP2 activity in MCF-7 BCC (Wang J.L. et al., 2000).

- Two invasive breast cancer cell lines (MDA-MB-231 and BT-549) were found to be more adherent and have greater migratory capacity on bone marrow fibroblasts than three non-invasive cell lines (MCF-7, T47D and BT-483). Inhibitors of matrix metalloproteases were able to attenuate the migration of MDA-MB-231 cells through bone marrow fibroblast monolayers, suggesting a role for these enzymes in the migration of breast cancer cells through bone marrow adherent layers. Co-culture of MDA-MB-231 cells and bone marrow fibroblasts resulted in augmentation of the levels of the matrix metalloproteases MMP-1 and MMP-2 in culture supernatants. Soluble factors produced by bone marrow fibroblasts were responsible for the increase in MMP-1 levels. However, maximal MMP-2 production was dependent on direct contract between the breast cancer cells and the bone marrow fibroblasts (Saad S. et al., 2000).

- MMP2 levels remained unchanged in MDA--MB-231 and MCF-7 BCC incubated under various oxygen concentrations for 24 h (Canning M.T. et al., 2001).

- CD147 (Basigin, EMMPRIN) is enriched oon the surface of tumor cells and is known to stimulate the production of MMPs by adjacent stromal cells. It has been found that CD147 engages in a homophilic interaction, predominantly through the first immunoglobulin domain. Anti-CD147 antibody 8G6 and recombinant CD147-Fc fusion protein markedly inhibited not only homophilic interaction, but also the production of secreted MMP-2 by MDA-MB-435 BCC and the MMP-2-dependent invasion of MDA-MB-435 cells through reconstituted basement-membrane Matrigel. Purified native CD147 induced the production of secreted MMP not only by dermal fibroblasts (MMP-1) but also by MDA-MB-435 cells themselves (MMP-2), suggesting homophilic CD147-binding may occur in the context of both heterotypic and homotypic cell-cell interactions. Purified deglycosylated CD147 failed to induce MMP-1 or MMP-2, but instead antagonized the MMP-1-inducing activity of purified native CD147 (Sun J. and Hemler M.E., 2001).

- MT1-MMP (MMP14) cleaves the N-terminall prodomain of pro-MMP-2 thus generating the activation intermediate that then matures into the fully active enzyme of MMP-2. It was found that coexpression of MT1-MMP and integrin alpha_Vbeta₃ in MCF-7 BCC specifically enhance in trans autocatalytic maturation of MMP-2. The association of MMP-2's C-terminal hemopexin-like domain with those molecules of integrin alpha_Vbeta₃ which are proximal to MT1-MMP facilitates MMP-2 maturation. Vitronectin, a specific ligand of integrin alpha_Vbeta₃, competitively blocked the integrin-dependent maturation of MMP-2. Immunofluorescence and immunoprecipitation studies supported clustering of MT1-MMP and integrin alpha_Vbeta₃ at discrete regions of the cell surface (Deryugina E.I. et al., 2001).

Tumors:
- Expression of mRNAs encoding MMP1, MMPP2 and MMP3, and of TIMP1 were studied in human mammary pathology by in situ hybridization and Northern blot analysis. Out of 6 benign lesions, 2 expressed MMP2 mRNAs. mRNAs encoding MMP1 and MMP3 were detectable in occasional stromal and tumor cells in 2 out of 17 carcinomas. Thirteen out of 17 cancers expressed MMP2 mRNA throughout the tumor in stromal cells close to noninvasive tumor clusters and well-differentiated invasive cancer cells. TIMP1 mRNA expression was detected in noninvasive and well-differentiated invasive tumor cells (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).

- Although MMP2 mRNA is preferentially eexpressed by stromal fibroblastic cells (Heppner K.J. et al., 1996), the mature form of the enzyme is located at the surface of cancer cells.

- MMP2 over-expression and activation haave been associated with the invasive potential of human tumors, notably breast carcinomas (Tryggvason K. et al., 1993; Heppner K.J. et al., 1996).

- In situ hybridization studies have shoown that the expression of MMP2 mRNA is mostly localized to tumor fibroblasts, while MMP9 mRNA is expressed by epithelial cells and macrophages (Polette M. et al., 1993, see MMP9).

- Angiogenesis depends on both cell adheesion and proteolytic mechanisms. MMP-2 and integrin alpha-V/beta-3 are functionally associated on the surface of angiogenic blood vessels. Brooks et al. (1998) found that a fragment of MMP-2, which comprises the C-terminal hemopexin-like domain (amino acids 445-635) and is termed PEX, prevents this enzyme from binding to alpha-V/beta-3 and blocks cell surface collagenolytic activity in melanoma and endothelial cells. PEX blocks MMP-2 activity on the chick chorioallantoic membrane where it disrupts angiogenesis and tumor growth. Brooks et al. (1998) also found that a naturally occurring form of PEX can be detected in vivo in conjunction with alpha-V/beta-3 expression in tumors and during developmental retinal neovascularization. Levels of PEX in these vascularized tissues suggest that it interacts with endothelial cell alpha-V/beta-3 where it serves as a natural inhibitor of MMP-2 activity, thereby regulating the invasive behavior of new blood vessels. The authors concluded that recombinant PEX may provide a potentially novel therapeutic approach for diseases associated with neovascularization.

- 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, MMP2 was meassured in paired tumour and normal tissue samples from 43 breast cancer patients. Latent MMP2 was found in 100% breast tumour samples and 100% normal breast, but the amount of the enzyme was significantly greater in tumour tissue than than in the corresponding normal tissue samples. Active MMP2 was expressed in 98% breast tumours and 49% normal breast samples (Garbett E.A. et al., 1999).

- Tumor cells interact with stromal cellls via soluble or cell-bound factors, including EMMPRIN/CD147/basigin (BSG), stimulating the production of MMPs. EMMPRIN protein was detected by immunohistochemistry prominently in malignant proliferations of the breast and the lung. It was present at the surface of both tumor epithelial and peritumor stromal cells. that the same peritumor stromal cells strongly expressed MMP-2 (Caudroy S. et al., 1999).

- the prognostic value of matrix metallooproteinase-2 (MMP-2) and age was evaluated in 108 premenopausal, node-positive breast carcinoma patients treated with an adjuvant chemotherapy. Expression of MMP-2 protein was studied in paraffin-embedded tissue sections from primary tumors by using specific MMP-2 monoclonal antibody in an immunohistochemical staining. Age less than 40 years predicted 5-year recurrence free survival (RFS) as unfavorable, being 74% in patients 41-49 years of age and 54% in those under age 40 (p = 0.02). The 5-year RFS rate was 85% in patients with an MMP-2 negative primary tumor while it was 65% in the MMP-2 positive patient group. This difference was not, however, statistically significant (p = 0.07). Correlation between hematogenous metastasis and MMP-2 positivity in breast carcinoma was demonstrated for the first time (p = 0.03). A risk group for a relapse was identified using MMP-2 immunohistochemistry and age. The RFS rate in patients less than 40 years with an MMP-2 positive primary tumor was only 50% while it was 74% in other premenopausal patients (p = 0.007) (Talvensaari-Mattila 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 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).

- In 1348 node-positive (NPBC) and node--negative (NNBC) breast cancers diagnosed between 1980 and 1986 and with a minimum follow-up of 5.2 years, cathepsin D (CTSD) expression was assessed by immunohistochemistry on archival material using a polyclonal antibody. Cancer cells expressed CTSD (more than 10% cells expressing CD) in 38.9% of cases and reactive stromal cells in 43.6%. CTSD expression by reactive stromal cells, and not cancer cells, correlated with several factors of poor prognosis by cancer cells. A strong association was also found with expression of other proteases (stromelysin-3/MMP11, gelatinase A/MMP2, and urokinase plasminogen activator/PLAU) by these same reactive stromal cells (Tetu B. et al., 1999).

- The expression patterns of MMP-1, -2, and -3 were determined by in situ hybridization in normal breast tissue (n=6), fibrocystic disease (n=20), five cases of which contained radial scars, lobular carcinoma in situ (CLIS; n=5), ductal carcinoma in situ (DCIS; n=9) and invasive carcinomas (n=24). Only a few cells displayed MMP-1- and MMP-2-specific labeling in normal breast tissue and fibrocystic disease. Noninvasive ductal carcinomas showed elevated MMP-2 transcript levels in peritumor stromal cells in the absence of significant MMP-1 specific signals. In general, compared with adjacent normal breast tissue, a gradual increase of MMP-2 was found in noninvasive to invasive cancers. Invasive ductal and lobular carcinomas displayed co-expression of MMP-1 and MMP-2 by stromal cells, mainly of the invasion front, with high signal intensity particularly in high-grade invasive carcinomas. Tumor cells and peritumor stroma showed low MMP-3 transcript levels, especially in medullary carcinomas (Brummer O. et al., 1999).

- 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).

- EMMPRIN (CD147, basigin) is thought too stimulate fibroblasts to produce the zymogen pro-MMP-2. The membrane type 1-matrix metalloproteinase (MT1-MMP, MMP14) is thought to assist in tumor invasion and metastasis by activating pro-MMP-2. The mRNA expression pattern of MT1-MMP, MMP-2, and EMMPRIN was studied in 18 breast tumor samples by in situ hybridization. MMP-2, MT1-MMP, and EMMPRIN mRNA expression were detected in all of the carcinomas. The MMP-2 mRNA expression was mainly localized to stromal cells at moderate to high levels surrounding the invading carcinoma cells but was also seen in single cells at low levels in in situ lesions and in some normal glandular cells. MT1-MMP and EMMPRIN were expressed in all of the carcinomas and were mainly localized to tumor cells; but they were also seen to some extent in single cells at low levels in in situ lesions and in normal glandular cells. No differences in levels of expression for MMP-2, MT1-MMP, or EMMPRIN were seen in patients who survived compared to patients who died from metastatic disease (Dalberg K. et al., 2000).

- 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).

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)
Brummer O. et al. (1999) Matrix-metalloproteinases 1, 2, and 3 and their tissue inhibitors 1 and 2 in benign and malignant breast lesions: an in situ hybridization study. Virchows Arch. 435, 566-573. (PubMed)
Canning M.T. et al. (2001) Oxygen-mediated regulation of gelatinase and tissue inhibitor of metalloproteinases-1 expression by invasive cells. Exp. Cell. Res. 267, 88-94. (PubMed)
Caudroy S. et al. (1999) Expression of the extracellular matrix metalloproteinase inducer (EMMPRIN) and the matrix metalloproteinase-2 in bronchopulmonary and breast lesions. J. Histochem. Cytochem. 47, 1575-1580. (PubMed)
Dalberg K. et al. (2000) Gelatinase A, membrane type 1 matrix metalloproteinase, and extracellular matrix metalloproteinase inducer mRNA expression: correlation with invasive growth of breast cancer. World J. Surg. 24, 334-340. (PubMed)
Deryugina E.I. et al. (2001) MT1-MMP initiates activation of pro-MMP-2 and integrin alphavbeta3 promotes maturation of MMP-2 in breast carcinoma cells. Exp. Cell. Res. 263, 209-223. (PubMed)
Garbett E.A. et al. (1999) Proteolysis in human breast and colorectal cancer. Br. J. Cancer 81, 287-293. (PubMed)
Gilles C. et al. (1998) SPARC/osteonectin induces matrix metalloproteinase 2 activation in human breast cancer cell lines. Cancer Res. 58, 5529-5536. (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)
Heppner K.J. et al. (1996) Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response. Am. J. Pathol. 149, 273-282. (PubMed)
Huhtala P. et al. (1990) Structure of the human type IV collagenase gene. J. Biol. Chem. 265, 11077-11082. (PubMed)
Huhtala P. et al. (1990) Completion of the primary structure of the human type IV collagenase preproenzyme and assignment of the gene (CLG4) to the q21 region of chromosome 16. Genomics 6, 554-559. (PubMed)
Ito A. et al. (1995) Co-culture of human breast adenocarcinoma MCF-7 cells and human dermal fibroblasts enhances the production of matrix metalloproteinases 1, 2 and 3 in fibroblasts. Br. J. Cancer 71, 1039-1045.(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)
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)
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)
Saad S. et al. (2000) Induction of matrix metalloproteinases MMP-1 and MMP-2 by co-culture of breast cancer cells and bone marrow fibroblasts. Breast Cancer Res. Treat. 63, 105-115. (PubMed)
Sato H. et al. (1994) A matrix metalloproteinase expressed on the surface of invasive tumor cells. Nature 370, 61-65. (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)
Sugiura T. and Berditchevski F. (1999) Function of alpha3beta1-tetraspanin protein complexes in tumor cell invasion. Evidence for the role of the complexes in production of matrix metalloproteinase 2 (MMP-2). J. Cell. Biol. 146, 1375-1389. (PubMed)
Sun J. and Hemler M.E. (2001) Regulation of MMP-1 and MMP-2 production through CD147/extracellular matrix metalloproteinase inducer interactions. Cancer Res. 61, 2276-2281. (PubMed)
Talvensaari-Mattila A. et al. (1999) MMP-2 positivity and age less than 40 years increases the risk for recurrence in premenopausal patients with node-positive breast carcinoma. Breast Cancer Res. Treat. 58, 287-293. (PubMed)
Tetu B. et al. (1999) Cathepsin D expression by cancer and stromal cells in breast cancer: an immunohistochemical study of 1348 cases. Breast Cancer Res. Treat. 55, 137-147. (PubMed)
Tryggvason K. et al. (1993) Type IV collagenases in invasive tumors. Breast Cancer Res. Treat. 24, 209-218. (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)
Wang J.L. et al. (2000) Gamma-irradiation induces matrix metalloproteinase II expression in a p53-dependent manner. Mol. Carcinog. 27, 252-258. (PubMed)

Genome Database data (GDB Access Number: 120592)
GeneCard data (MMP2)
UniGene data (Hs.111301)
OMIM data (ID = 120360)
LocusLink data (LocusID = 4313)
Swiss-Prot (ID = P08253)


MMP1, MMP3, MMP7, MMP9, MMP11, MMP13, MMP14, MMP15, MMP16, MMP17, TIMP1, TIMP2, TIMP3, TIMP4