Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gelatin viscous solution containing mitomycin C (MMC) was prepared and its antitumor effects were evaluated toward sarcoma-180 (S-180) ascite tumor bearing mice. Among various gelatin concentrations, 3% and 5% gelatin solutions potentiated the antitumor effects of MMC (7.5 mg/kg) against S-180 bearing mice. A "bell-shaped" profile was observed between % release of MMC from the gelatin matrix and increased life span (ILS) %. On the other hand, in the case of 10 mg/kg dose of MMC, 7.5% and 10% gelatin solutions potentiated its antitumor effects. At both doses of 7.5 and 10 mg/kg of MMC, decrease in body weight of mice after intraperitoneal administration of MMC were suppressed by increasing the concentration of gelatin. To confirm a possible mechanism for increase in ILS % after intraperitoneal (i.p.) administration of the gelatin viscous solution containing MMC, we examined the pharmacokinetics of MMC after i.p. administration into rats. By the use of 3 % gelatin solution, mean residence time (MRT) and Tmax values were significantly prolonged, and Cmax was decreased as compared with the administration of MMC solution. These results suggested that the enhancement of antitumor effect of MMC by the gelatin viscous solution could be caused by decrease in the clearance rate of MMC from the peritoneal cavity to systemic circulation due to decreasing its diffusivity in gelatin matrix.
 ...
PMID:Pharmacokinetics of mitomycin C (MMC) after intraperitoneal administration of MMC-gelatin gel and its anti-tumor effects against sarcoma-180 bearing mice. 916 85

Intraportal vein injection of highly metastatic L5 cells consistently resulted in liver metastases (increases in the number of tumor colonies in the liver), whereas inoculation of P cells rarely did. L5 cells invaded the basement membrane Matrigel in greater numbers than did P cells, suggesting that the metastatic potential of L5 cells is partly related to enhanced invasive properties. The enhanced adhesion of L5 cells to fibronectin-, laminin- and Matrigel-coated substrates, as well as their haptotactic migration to fribronectin, may be associated with the preferential expression of VLA-2 and VLA-4 integrins on the surface of these cells detected by flow cytometry. Gelatin zymograms showed that the degradative activity of 72-kD gelatinases was greater in L5 cells than P cells. These results indicate that, in addition to adhesiveness and motility, the invasive ability of L5 cells may also be attributed to enhanced gelatinolytic activity. L5 cells grew more rapidly than P cells in vitro. Thus, an experimental model using highly metastatic colon 26 L5 cells would be useful for analyzing the molecular mechanism of liver metastasis and for evaluating the efficacy of treatment of occult micrometastases which may already have been disseminated at the time of surgery.
Tumour Biol 1997
PMID:Characterization of a liver metastatic variant of murine colon 26 carcinoma cells. 922 9

Several methods have been developed for the measurement of gelatinase activity from various tissues using detergent extraction. Gelatin-affinity chromatography has been employed for the large-scale purification of gelatinases from conditioned medium obtained from cultured cells. The objective of this paper was to develop a rapid method whereby gelatinase activity could be extracted from regional brain tissues without tedious, intervening purification steps. After Triton X-100 extraction and gelatin-Sepharose 4B purification of rat brain tissue extracts, two major activities were observed on gelatin zymograms. These were identified as gelatinase A and B using co-migration with astrocyte-derived enzymes and inhibition of activity by tissue inhibitor of matrix metalloproteinase-1 (TIMP-1). The non-ionic detergents, Triton X-100 and 3-[(3-cholamidopropyl)dimethylammonio]-1-propane-sulfonate (CHAPS) were equally effective in extracting activities from brain tissue. Little difference in recovery was observed among 0.1, 1 and 10% concentrations of Triton X-100. The method developed here was capable of recovering gelatinase activities from rat brain tissue over a 4-10-fold range using gelatin zymography for the measurement of activity. It is possible that this method may be modified for the measurement of gelatinases in tissues such as biopsy samples of gliomas or astrocytomas or other cancers where gelatinases are thought to play a role in tumor invasion and/or metastasis.
 ...
PMID:Zymographic measurement of gelatinase activity in brain tissue after detergent extraction and affinity-support purification. 933 34

Theaflavin and theaflavin digallate, which are components of black tea were examined by in vitro invasion assay with mouse Lewis lung carcinoma LL2-Lu3 cells, which are highly metastatic. The compounds inhibited invasion by the tumor cells. Gelatin zymography showed that the cells secreted matrix metalloproteinases (MMPs), probably including MMP-2 and MMP-9, which may be involved in tumor cell invasion and metastasis. Theaflavin and theaflavin digallate also inhibited MMPs from the culture medium of these tumor cells, as did (-)-epigallocatechin gallate. These results suggest that theaflavin, theaflavin digallate, and (-)-epigallocatechin gallate inhibit tumor cell invasion by inhibiting type IV collagenases of the LL2-Lu3 cells.
 ...
PMID:Inhibition of collagenases from mouse lung carcinoma cells by green tea catechins and black tea theaflavins. 933 52

Degradation of extracellular matrix takes place in areas of cell-matrix contacts and is partly carried out by the action of matrix metalloproteinases (MMP). MMP-2 is a member of the MMP family that has been associated with breast-cancer metastasis. In the present study, we investigated the association of MMP-2 to the surface of breast-cancer cells and revealed an MMP-2-binding site that is expressed on sparsely plated cells and which is progressively lost as the cells approach confluence. Gelatin zymography, immunostaining and flow cytometry of MDA-MB-231 cells from sparse cultures demonstrated binding both of latent and of activated exogenous MMP-2, while little or no binding of MMP-2 was observed in confluent culture. Analysis of the expression of MTI-MMP, TIMP-2 and alpha(v) integrin, 3 proteins shown to play a role in cell-surface association of MMP-2, revealed enhanced levels of these proteins in confluent MDA-MB-231 cells. Thus, the reduced MMP-2 binding to confluent cells is not related to a deficiency in these MMP-2-binding proteins. Taken together, these studies suggest that MMP-2 binding to the surface of breast-cancer cells is regulated by cell-cell interactions and that tumor cells invading from the main tumor mass can up-regulate their MMP-2-binding capacity to acquire greater invasive capacity.
 ...
PMID:Density-dependent regulation of cell-surface association of matrix metalloproteinase-2 (MMP-2) in breast-carcinoma cells. 946 17

During invasion and metastasis, cancer cells interact closely with the extracellular matrix molecules by attachment, degradation, and migration. We demonstrated previously the local degradation of fluorescently labeled gelatin matrix by cancer cells at invasive membrane protrusions, called invadopodia. Using the newly developed quantitative fluorescence-activated cell sorting-phagocytosis assay and image analysis of localized degradation of fluorescently labeled matrix, we document here that degradation and site-specific removal of cross-linked gelatin matrix is correlated with the extent of phagocytosis in human breast cancer cells. A higher phagocytic capacity is generally associated with increasing invasiveness, documented in other invasion and motility assays as well. Gelatin phagocytosis is time and cell density dependent, and it is mediated by the actin cytoskeleton. Most of the intracellular gelatin is routed to actively acidified vesicles, as demonstrated by the fluorescent colocalization of gelatin with acidic vesicles, indicating the intracellular degradation of the phagocytosed matrix in lysosomes. We show here that normal intracellular routing is blocked after treatment with acidification inhibitors. In addition, the need for partial proteolytic degradation of the matrix prior to phagocytosis is demonstrated by the inhibition of gelatin phagocytosis with different serine and metalloproteinase inhibitors and its stimulation by conditioned medium containing the matrix metalloproteinases MMP-2 and MMP-9. Our results demonstrate that phagocytosis of extracellular matrix is an inherent feature of breast tumor cells that correlates with and may even directly contribute to their invasive capacity. This assay is useful for screening and evaluating potential anti-invasive agents because it is fast, reproducible, and versatile.
 ...
PMID:Phagocytosis of cross-linked gelatin matrix by human breast carcinoma cells correlates with their invasive capacity. 951 43

The binding of two matrix metalloproteinases (MMP) to fibrin was evaluated. MMP-2 (72-kDa) and MMP-9 (92-, 130-, and 225-kDa) were selected since both contain a fibronectin-like region and fibronectin binds fibrin. Gelatin zymography indicated selective and dose dependent binding of MMP-9 to fibrin. No MMP-2 binding to fibrin occurred. Densitometry revealed that the 130- and 225-kDa forms demonstrated similar sigmoidal binding profiles whereas 92-kDa uptake was hyperbolic. Fibronectin and TIMP-1 competition studies indicated that the fibronectin and C-terminal MMP-9 domains, respectively, were not involved with fibrin binding. The MMP-9 collagen-like region may be of regulatory significance since type I and II fibrillar and type IV basement membrane collagens demonstrated fibrin binding. During fibrinolysis, latent fibrin-bound MMP-9 was processed to lower molecular weight forms consistent with proteolytic activation. This process was inhibited by epsilon-aminocaproic acid, indicating a plasmin-dependent pathway. The significance of these findings to procoagulant activity and MMP-mediated extracellular matrix destruction during inflammation and tumor invasion and metastasis is discussed.
 ...
PMID:Binding of latent matrix metalloproteinase 9 to fibrin: activation via a plasmin-dependent pathway. 960 16

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is expressed both in carcinoma cells and in surrounding stromal fibroblasts. MT1-MMP localizes to the surface of tumor cells and is thought to play an important role in tumor invasion. To analyze the mechanism of MT1-MMP gene expression in epithelial tumor cells, the dog kidney epithelial cell line Madin-Darby canine kidney (MDCK) was transformed by oncogenes, including v-src, and expression of MT1-MMP was examined. Transformation of MDCK cells with v-src resulted in loss of cell-to-cell contacts and morphological change. Expression of MT1-MMP in v-src-transformed cells was identified by Northern and Western blotting. Gelatin zymography analysis showed that progelatinase A in the culture medium was processed from latent to activated form by MDCK cells transformed with v-src. The MDCK cells transformed by v-src were tumorigenic in the subcutis (ectopic) and kidney (orthotopic) of nude mice and spontaneously metastasized to the lung after orthotopic implantation. These results suggest that MT1-MMP induced by v-src transformation may promote invasiveness of transformed cells.
 ...
PMID:Transformation of epithelial Madin-Darby canine kidney cells with p60(v-src) induces expression of membrane-type 1 matrix metalloproteinase and invasiveness. 960 72

Gelatin binds to fibronectin with a high affinity although the fibronectin-binding components have not been located. Fibronectin plays an important role in tumor cell metastasis and gelatin may have a profound effect on the metastatic process. In this study, fractionated acid-washed gelatin was cleaved with trypsin and resultant peptides fractionated by fibronectin-Sepharose affinity chromatography. After further purification using size exclusion HPLC and then reverse-phase HPLC, two unique peptides were obtained and sequenced. The binding affinities of these two peptides to fibronectin were evaluated by an ELISA method developed during this study and compared with the gelatin. Both possessed significantly higher binding affinities to fibronectin than gelatin alone.
 ...
PMID:Fibronectin-binding peptides. I. Isolation and characterization of two unique fibronectin-binding peptides from gelatin. 965 32

Clone C5 of the human colon adenocarcinoma LoVo cell line was subcutaneously injected with or without exogenous laminin-1 (EHS laminin) into immunosuppressed newborn rats. Cultures were initiated from lung metastases obtained with or without laminin-1 and gave rise to the C5 sublines LM and M4, respectively. The LM subline was mainly composed of spreading cells whereas most C5 and M4 cells remained round and aggregated. The mesenchymal marker vimentin was expressed by very rare C5 and M4 cells (< 1%), and by many LM cells (about 35%). On the opposite, the epithelial markers villin and dipeptidylpeptidase IV were well expressed by C5 cells but not by LM cells. In in vitro migration and invasion assays, LM cells migrated and invaded basement membrane extract twice as much as the parental C5 clone and the M4 subline, probably in association with vimentin-expressing cells, because invasion of basement membrane extract Matrigel by LM cells gave rise to 100% vimentin-positive cells (sublines LM 22, LM 23 and LM 24). When subcutaneously injected, C5 cells induced tumors limited by an interrupted but well organized basement membrane, whereas LM cells induced tumor masses, occasionally limited by a very irregular basement membrane, as observed when C5 cells were injected with laminin-1. Gelatin zymographic analysis clearly showed an increased expression of matrix metalloproteinase-2 by LM cells. Our results suggest a specific role of laminin-1 on the in vivo proliferation of highly invasive vimentin-expressing colon carcinoma cells. This proliferation may result from the initial interaction of C5 cells with large amounts of laminin-1, leading to a selection of vimentin-expressing cells during the metastatic cascade.
 ...
PMID:Loss of epithelial differentiation markers and acquisition of vimentin expression after xenograft with laminin-1 enhance migratory and invasive abilities of human colon cancer cells LoVo C5. 969 8


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>