Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Papain-immunized mice possess serum antibodies which cross-react with cathepsin-B- and cathepsin-H-like endopeptidases isolated from B16 melanoma cells. The growth rate, invasion and metastasis of both the B16 melanoma and the Lewis lung carcinoma were inhibited in mice immunized with papain. These animals presented an increased mean survival time as compared to the tumor-bearing nonimmunized controls. Quantitative microscopy suggested that vasodilation and edema, associated with tumor invasion, are, at least partially, sustained by proteolytic enzymes, being strongly reduced when tumor cells were inoculated in papain-immunized mice.
Invasion Metastasis 1990
PMID:Inhibition of tumor growth, invasion and metastasis in papain-immunized mice. 213 72

Lysosomal cysteine proteinases, cathepsins B, H and L, and tumor cathepsin-B-like protease, are capable of digesting bovine lens capsule, a typical basement membrane, in vitro. Cathepsins L and H proved most active in the pH range 5.0-7.0, whereas cathepsin B and cathepsin B-like protease showed greatest activity at pH 3.0. The process was slow and involved binding of the proteases to the basement membrane. These proteases, of which some are produced by malignant cells, may contribute to tumor spread and progression to metastatic disease.
 ...
PMID:[Digestion in vitro of basal membrane, bovine lens capsule, by human liver lysosome cathepsins B, H and L and ascitic fluid tumor cathepsin B from ovarian adenocarcinoma]. 229 Jun 99

Proteolytic and sialyltransferase activities were determined in extracts of 65 human primary breast tumors, 6 lymph node metastases, 6 fibroadenomas and 27 normal tissues. Using proteins and synthetic selective substrates, we observed the presence of collagen-peptidases, plasminogen activator, cathepsin-B and cathepsin-D-like enzymes, and sialyltransferase. No active or trypsin-activatable type-IV collagenase activity was detected. Although individual variations between tumors were large, proteinase and sialyltransferase contents were significantly elevated in malignant breast tissues. Enzyme activities were found to be related to the epithelial volume of the tumor. No significant correlation was found between the proteinase or sialyltransferase activities and the degree of differentiation of the tumor cells, or the degree to which tumors had metastasized to regional lymph nodes. Since large variations of enzyme levels apparently reflect the heterogeneity of epithelial cell densities in tumor samples, proteolytic or sialyltransferase activities cannot therefore be used as a measure of quantitative evaluation of invasive properties in breast cancer.
 ...
PMID:Proteinases and sialyltransferase in human breast tumors. 632 71

Expression of an acidic lysosomal protease, cathepsin-D (CD), was analysed immunohistochemically in a series of 151 breast carcinomas with special reference to its prognostic significance, Strong expression of CD was detected in 22% of cases. This intense expression was significantly associated with a number of established prognostic factors, including the non-ductal type of carcinoma (p = 0.0243) and metastases at the time of diagnosis (p = 0.0068). On the other hand, high expression of CD was not related to the lymph-node status, tumour size, ER/PR content or histological grade. Patients with CD overexpression has a significantly lower survival probability (p = 0.0478) than did the patients with low expression of this protease. The relationship between the high expression of CD and short disease-free survival was almost significant (p = 0.0519). Intense immunostaining of CD was associated with a significantly impaired disease outlook in patients with confirmed lymph node metastasis (N+) (p = 0.0137) but not in those with negative lymph nodes (N-) (p = 0.0620). In Cox's multivariate analysis, expression of CD had no independent prognostic value over the conventional prognostic factors. The results suggest that expression of CD is of borderline significance in evaluating the intrinsic malignancy of female breast cancer in general. The potential of CD as a prognostic factor in specific subgroups of breast cancers will be the subject of further studies.
 ...
PMID:Prognostic value of cathepsin-D expression in female breast cancer. 764 22

Degradation of the extracellular matrix is a prerequisite for acquisition of the invasive phenotype. Several proteinases released by invading tumor cells appear to participate in the focal degradation of extracellular matrix proteins. Using an enzyme-linked immunosorbent assay, enzymatic assays, Western and Northern blotting techniques, we determined whether increased levels of the cysteine protease cathepsin B correlated with the progression and invasion of human gliomas. The amount of cathepsin B activity and protein content were highest in glioblastomas, lower in anaplastic astrocytomas and lowest in normal brain tissue and low-grade gliomas. There were significantly higher amounts of M(r) 25,000 and 26,000 bands in glioblastoma and anaplastic astrocytoma than in normal brain and low-grade glioma tissue extracts as determined by Western blotting with anti-cathepsin antibodies. In addition, cathepsin B transcripts were overexpressed in anaplastic astrocytoma (about two- to three-fold), in glioblastoma (about eight- to 10-fold), compared with normal brain tissue and low-grade glioma. Immunohistochemical staining for cathepsin B showed intense immunoreactivity in tumor and endothelial cells of glioblastomas and anaplastic astrocytomas but only weak immunoreactivity in low-grade glioma and normal brain tissues. Therefore, we conclude that cathepsin B expression is greatest in highly malignant astrocytomas, especially in glioblastomas, and is correlated with the malignant progression of astrocytomas.
Clin Exp Metastasis 1995 Jan
PMID:Overexpression and localization of cathepsin B during the progression of human gliomas. 782 Sep 56

The expression of three lysosomal cysteine proteases was examined in a lowly metastatic, MCF-7 human breast cancer cell line and its highly metastatic, Adriamycin-resistant variant, MCF-7/AdrR. While levels of cathepsin H activity were similar in all cell lines at each stage of growth, intracellular cathepsin B and L activities were highest in MCF-7/AdrR. These high levels were accompanied by growth-related increases in acid/pepsin-activatable cathepsin activity in the culture medium. Analyses of endogenous cathepsin B inhibitor activity in control and heat-treated cell homogenates after fractionation by fast protein liquid chromatography suggested that alterations in cystatin-like, cysteine protease inhibitor activities contribute to increased levels of cathepsin activities in metastatic MCF-7/AdrR cells.
Invasion Metastasis 1993
PMID:Characterization of cysteine proteases and their endogenous inhibitors in MCF-7 and adriamycin-resistant MCF-7 human breast cancer cells. 786 Feb 23

The relationship between the Cathepsin-D concentration in breast cancer cytosols and clinical and histopathological characteristics of the tumours was investigated, including vascular invasion, histological type, histological grade, lymph node involvement and tumour size. The median cathepsin-D concentration of a series of 738 primary breast carcinomas was used to define "low" and "high" cathepsin-D. High cathepsin-D concentration was associated with peritumoral vascular invasion, with high grade infiltrating duct carcinomas, with tumours of > or = 2 diameter, and with metastases in the axillary lymph nodes. Low cathepsin-D concentration was associated with in-situ carcinomas.
 ...
PMID:Cathepsin-D in human breast cancer: correlation with vascular invasion and other clinical and histopathological characteristics. 829 25

It has been suggested that cathepsin D expression in stromal cells affects the prognosis of breast cancer. With reference to colon and breast cancer, this study verified cathepsin D immunostaining in epithelial and stromal cells of primary tumours and lymph-node metastases from 46 colorectal carcinomas. Eight of 46 cases (17%) were cathepsin D+ both in cancer and stromal cells. No staining was found either in cancer or stromal cells of the remaining cases. The results presented here suggest the possible paracrine influence of another diffusible factor produced by cancer cells which stimulates cathepsin D production in stromal and cancer cells.
 ...
PMID:The immunohistochemical expression of cathepsin D in colorectal cancer. 861 73

Increased levels of human cysteine proteases have been implicated in the progression of tumors from the premalignant to the malignant state. The physiological activities of these proteases are regulated by their interactions with specific inhibitors. To our knowledge there have been no previous reports about the cysteine protease inhibitors (CPIs) in human brain tumors. In the study reported here, we determined CPI activity during glioma progression and compared that with normal human brain tissue. We also determined CPI activities in meningioma and glioblastoma cell lines in vitro. This activity was significantly higher in normal brain tissue and low-grade glioma than in anaplastic astrocytoma and glioblastoma. CPI activity was significantly higher in benign and atypical meningioma cell extracts in comparison with those from malignant meningiomas and with those from glioblastoma cell lines. After several passages, one benign meningioma cell line showed reduced levels of CPI and increased levels of cathepsin. Our results suggest that decreases in the activities of CPI may contribute to the malignant properties of brain tumors.
Clin Exp Metastasis 1996 Sep
PMID:Expression of cysteine protease inhibitors in human gliomas and meningiomas. 887 8

Cells in tumors may be exposed to adverse conditions such as nutrient deprivation, acidic pH and hypoxia. It has been shown previously that exposure to hypoxia, acidosis and glucose starvation in vitro increases the experimental metastatic ability of murine KHT-LP1 sarcoma, SCC-VII squamous carcinoma and B16 melanoma cells. This effect was most marked when cells were allowed to recover under normal in vitro growth conditions before injection. In the present study we examined whether the invasive capacity of the cells could be influenced by these modifications of the cell microenvironment. We used Matrigel, a basement membrane-like preparation in a two-chamber invasion assay to address this issue. Both KHT-LP1 and SCC-VII murine cell lines showed an increased ability to invade through Matrigel after hypoxia, and glucose starvation, but there was no consistent change in invasive capacity following acidosis exposure. The results for hypoxia and glucose starvation are in agreement with our previous studies of metastatic ability for these cell lines and we confirmed this for KHT-LP1 cells exposed to hypoxia in the current study. In parallel with the invasion assays, we compared cathepsin (L + B) content of the cells in treated and control suspensions. The effect observed varied according to the cell line and the treatment received (hypoxia, glucose starvation). There was an increase of cathepsin content for KHT-LP1 cells exposed to hypoxia and this increase correlated well with the increase of the invasion ability through Matrigel. We did not observe any increase of cathepsin for hypoxia-treated SCC-VII or for KHT-LP1 and SCC-VII cells treated with glucose starvation. These results suggest that transient hypoxia and glucose starvation can increase the invasive ability of tumor cell lines and thus may cause tumor progression by facilitating the invasive step of the metastatic process. The increased levels of cathepsin (L + B) in the KHT-LP1 cells treated with hypoxia, compared to control non-treated cells, may play a part in this increased invasive capacity.
Clin Exp Metastasis 1997 Jan
PMID:Exposure to hypoxia, glucose starvation and acidosis: effect on invasive capacity of murine tumor cells and correlation with cathepsin (L + B) secretion. 900 2


1 2 3 4 Next >>