Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.17 (MMP-3)
 3,419 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A recognized model of tumor invasion requires cells to adhere to epithelial basement membrane and extracellular matrix components triggering release of proteases thus allowing cancer cells to invade the substrate. This adhesion is mediated by beta 1 integrins, a family of receptors to substrates such as collagen, laminin, and fibronectin. In order to study tumor invasion in follicular thyroid cancer (FTC), we used cell lines derived from a single patient's FTC primary tumor (FTC-133), neck lymph node metastases (FTC-236), and lung metastases (FTC-238). In vitro invasion as determined by the ability of the tumor cells to penetrate Matrigel was assessed by scanning electron microscopy. FTC-133 did not invade, FTC-236 was moderately invasive, and FTC-238 was highly invasive. Immunoprecipation with a monoclonal antibody to beta 1 integrin subunits and SDS-PAGE showed increased synthesis and flow cytometry showed increased expression of this subunit in FTC-236 and FTC-238 compared to FTC-133. Proteolytic activity was assessed by gelatin zymography. FTC-238 cell extract and conditioned media exhibited a more complex array of proteases consistent with activated type I collagenase and stromelysin compared to the less invasive clones, however 72 and 92 kd gelatinases consistent with type IV collagenases were present in the conditioned media from all three lines. In conclusion, in vitro invasion parallels in vivo metastasis by the source cells in the FTC-133/236/238 cell-lines. The ability to invade basement membrane preparation correlates with increased synthesis and expression of beta 1 integrins and activation of tumor proteases.
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PMID:Invasion by cultured human follicular thyroid cancer correlates with increased beta 1 integrins and production of proteases. 138 45

Specific antisera for the connective tissue metalloproteinases, collagenase, gelatinase (type IV collagenase) and stromelysin were used to study their respective localizations in both rabbit primary VX2 tumours and in lung metastatic deposits (frozen immediately after excision). Collagenase was found within some cells of the primary tumour and also bound to the extracellular matrix at discrete sites. Previous studies suggest that this matrix staining represents active enzyme. Stromelysin and gelatinase had a more limited distribution, particularly the latter, but both showed cell and matrix staining. In the lung metastases collagenase and stromelysin occurred less frequently, although both cell and matrix staining were observed; gelatinase was not seen. When rabbit VX2 cells were transplanted into nude mice they grew as a discrete nodule. Cells within this nodule stained with the antiserum to collagenase, which recognizes rabbit but not mouse enzyme, and thus demonstrated that cells of tumoural origin synthesize collagenase in vivo. Stromelysin was also co-localized with collagenase in some tumour cells.
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PMID:Collagenase is expressed by rabbit VX2 tumour cells in syngeneic and xenogeneic hosts. 255 Jul 52

Cell lines with high metastatic capacity to the lung were established by sequential passage of a human pancreatic cancer cell line (SUIT-2) through the lung of a nude mouse, via the lateral tail vein and from a subcutaneous inoculum. Cells of the parental SUIT-2 and sublines S2-VPx (x-cycle selection from SUIT-2 cells, by Vein-Pulmonary metastasis-culture) and S2-CPx (x-cycle selection, by Cutis-Pulmonary metastasis-culture) were injected intravenously or subcutaneously into nude mice to produce experimental or spontaneous lung metastasis. The S2-VP10 cell line produced pulmonary metastases in 100% of the nude mice, when injected intravenously. It failed, however, to produce more lung colonies than its parent cell line, when injected subcutaneously. The S2-CP8 cell line produced extensive pulmonary metastases in 100% of the nude mice, when injected either intravenously or subcutaneously. This study indicates that the nude mouse provided a good model for in vivo selection of metastatic cells from SUIT-2 cells both experimentally and spontaneously, and that the SUIT-2, S2-VPx, and S2-CPx cell lines will be valuable in the study of human cancer metastasis. We previously reported high levels of ezrin expression in the S2-VP10 and S2-CP8 cell lines. Here we show that these cell lines exhibit a greater capacity to invade or attach to various extracellular matrix components than the parent SUIT-2 cells. The S2-CP8 cell lines also exhibit greater level of type-I and type-IV collagen-degrading activity than the parent SUIT-2 cell line and the S2-VP10 cell line, which shows similar collagen-degrading activity to the parent SUIT-2 cells. In RT-PCR studies, SUIT-2, S2-CP8 and S2-VP10 cell lines constitutively expressed many matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP7, MMP-9, MMP-10 and MMP-14). These results suggest that some parameters that enhance adhesion and invasion are important to both experimental and spontaneous metastasis and the collagen degrading enzymes are predicted to play a key-role during spontaneous metastasis.
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PMID:High collagenolytic activity in spontaneously highly metastatic variants derived from a human pancreatic cancer cell line (SUIT-2) in nude mice. 1168 61

Elevated expression of matrix metalloproteinase-3 (MMP-3/stromelysin-1) is associated with a variety of tumor types, although its in vivo functional role remains unclear. In human and murine squamous cell carcinoma (SCC), MMP-3 is expressed in the stromal compartment at all of the stages of tumor progression and is expressed by the malignant epithelial cells in late-stage, highly invasive tumors. To elucidate whether MMP-3 plays a causal role during SCC, wild-type and MMP-3 null mice were subjected to chemical carcinogenesis procedures by topical application of either the complete carcinogen 1-methyl-3-nitro-1-nitroso-guanidine or two-stage initiation and promotion with 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate. Contrasting with our expectations, tumors originating on MMP-3 null mice had enhanced initial tumor growth rates as compared with control animals, although there was no difference in tumor onset or incidence. This elevated rate in growth was coupled with an elevated proliferative index and a reduced vasculature density but with no significant effect on apoptosis. Tumors from MMP-3 null mice had a prevalence of undifferentiated spindle tumors as compared with controls, which was concomitant with a higher percentage of MMP-3 null mice evidencing surface lung metastases. Tumor progression in MMP-3 null mice was inversely associated with leukocyte infiltration, in which an overall reduction in tumor-associated macrophages and neutrophils was evident. We propose that MMP-3 is expressed as a protective response and plays an important role in host defense during SCC tumorigenesis.
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PMID:A protective role for matrix metalloproteinase-3 in squamous cell carcinoma. 1546 88