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

In tumor tissue specimens of 27 primary and 17 secondary glioblastomas and the precursor lesions, the immunohistochemical expression patterns of the membrane protein CD44s, the basal lamina proteins laminin, collagen IV, and fibronectin, the lectin galectin-3 recognizing tenascin and N-CAM as well as of the matrix-degrading enzymes matrix metalloproteinase MMP-2 and MMP-9, and cathepsin D were studied. Besides expression of basal lamina proteins in vessels, all glioblastomas and the precursor lesions showed strong immunoreactivity of CD44s, tenascin, galectin-3, and N-CAM which were restricted to solid tumor masses. Present in solid tumor areas, MMP-2, MMP-9 and cathepsin D were also strongly expressed by single tumors cells invading adjacent brain tissue at the infiltrative margin. Neither the expression pattern in primary and secondary glioblastomas nor in the precursor tumors revealed significant differences. There was also no intraindividual constant expression pattern during glioma progression or correlation with malignancy. Restricted expression of CD44s, galectin-3, tenascin and N-CAM in solid tumor masses seems to contribute to homotypic tumor cell adhesion while single tumor cells abolish this expression profile and acquire invasive activities by expression of cathepsin D, MMP-2 and MMP-9.
Invasion Metastasis
PMID:Expression of adhesion factors and degrading proteins in primary and secondary glioblastomas and their precursor tumors. 1072 72

To search for reliable predictors for lymph node metastasis, we immunohistochemically analyzed surgically resected gastric cancer specimens that showed invasion of submucosa (sm) and muscularis propria (mp) of the tumor. The analysis investigated cathepsin D and Ki-67 expression in 136 specimens that were divided into an sm1/sm2 group and an sm3/mp group. In sm1/sm2 group, the incidence of lymph node metastases was significantly higher in tumors with high Ki-67 labeling index (LI) (44%) than in those with low Ki-67 LI (0%). In sm3/mp group, the incidence of lymph node metastases was significantly higher in cathepsin D-positive (56%) and high Ki-67 LI tumors (64%) than in cathepsin D-negative (33%) and low Ki-67 LI (33%). Combined analysis of cathesin D expression and Ki-67 LI correlated strongly with lymph node metastases. No lesions with cathepsin D-negative expression and low Ki-67 LI had lymph node metastases in either group. Cathepsin D and Ki-67 expression may be useful predictors for lymph node metastases in gastric cancer with sm and mp invasion. As predictors, they can identify lesions without lymph node metastases and indicate lesions not needing additional treatment after endoscopic mucosal resection and laparoscopic gastrectomy.
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PMID:Predictive value of cathepsin D and Ki-67 expression at the deepest penetration site for lymph node metastases in gastric cancer. 1085 31

Angiostatin, a potent endogenous inhibitor of angiogenesis, is generated by cancer-mediated proteolysis of plasminogen. The culture medium of human prostate carcinoma cells, when incubated with plasminogen at a variety of pH values, generated angiostatic peptides and miniplasminogen. The enzyme(s) responsible for this reaction was purified and identified as procathepsin D. The purified procathepsin D, as well as cathepsin D, generated two angiostatic peptides having the same NH(2)-terminal amino acid sequences and comprising kringles 1-4 of plasminogen in the pH range of 3.0-6.8, most strongly at pH 4.0 in vitro. This reaction required the concomitant conversion of procathepsin D to catalytically active pseudocathepsin D. The conversion of pseudocathepsin D to the mature cathepsin D was not observed by the prolonged incubation. The affinity-purified angiostatic peptides inhibited angiogenesis both in vitro and in vivo. Importantly, procathepsin D secreted by human breast carcinoma cells showed a significantly lower angiostatin-generating activity than that by human prostate carcinoma cells. Since deglycosylated procathepsin D from both prostate and breast carcinoma cells exhibited a similar low angiostatin-generating activity, this discrepancy appeared to be attributed to the difference in carbohydrate structures of procathepsin D molecules between the two cell types. The seminal vesicle fluid from patients with prostate carcinoma contained the mature cathepsin D and procathepsin D, but not pseudocathepsin D, suggesting that pseudocathepsin D is not a normal intermediate of procathepsin D processing in vivo. The present study provides evidence for the first time that cathepsin D secreted by human prostate carcinoma cells is responsible for angiostatin generation, thereby causing the prevention of tumor growth and angiogenesis-dependent growth of metastases.
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PMID:Angiostatin generation by cathepsin D secreted by human prostate carcinoma cells. 1098 84

CD44 is a cell adhesion molecule involved in tumour growth and progression. This study was undertaken to evaluate the expression of CD44 standard protein in a series of 54 colorectal adenocarcinomas in correlation with cathepsin D immunoreactivity and some other clinicopathological variables. Formalin-fixed and paraffin-embedded tissues were investigated with anti-CD44 standard protein and anti-cathepsin D antibody. Immunolocalisation of CD44 protein and cathepsin D was performed using LSAB method. 13 (41.9%) out of 31 carcinomas without lymph-node metastases had positive CD44 expression, whereas only 6 (26.1%) out of 23 carcinomas with lymph-node metastases were found positive for CD44 expression. CD44 expression in carcinomas was positively correlated with tumour cells cathepsin D (p<0.01) immunostaining. statistically significant correlation was found between the expression of CD44 standard protein and the tumour site, age and sex of the patients. These results suggest that the standard-type CD44 protein lymph-node metastases, probably with cooperation of cathepsin D.
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PMID:CD44 expression in colorectal cancer. An immunohistochemical study including correlation with cathepsin D immunoreactivity and some tumour clinicopathological features. 1182 May 82

Although it has been suggested that tumour budding at the invasive edge of colorectal cancer is an important prognostic factor its biological significance for tumour progression is still to be evaluated. The aim of the study was to correlate tumour budding intensity with cathepsin D expression and some other clinicopathological variables of presumed or established prognostic value. 48 patients with colorectal cancer at pT3 stage, G2 grade of histological differentiation and tumour budding at the invasive edge were evaluated. Colorectal tumours were investigated for cathepsin D expression by immunohistochemistry of formalin-fixed and paraffin embedded tissues. There was no statistically significant relationships between tumour budding intensity grade and primary tumour cathepsin D expression, stromal cell cathepsin D expression and histochemical immunostaining of cathepsin D in rumour budding at its invasive edge. The tumour budding intensity was not associated with lymph node status, tumour site, peritumoral inflammatory response as well as the patient's age and sex. The results of this study suggest that intensity of tumour budds formation at the invasive margin of colorectal cancer is not associated with presumed or established prognostic factors such as lymph node metastases, and peritumoural inflammatory reaction as well as cathepsin D expression.
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PMID:Tumour budding intensity in relation to cathepsin D expression and some clinicopathological features of colorectal cancer. 1182 May 92

Biologic features that distinguish follicular adenomas (FAs), minimally invasive follicular carcinomas (MICs), and extensively invasive follicular carcinomas (EICs) of the thyroid gland are not well understood. Endogenous proteases, including cathepsin B (CB) and cathepsin D (CD), have been linked to tumor progression in other malignancies and may be important in the different biologic behavior of these follicular thyroidal lesions. Archival paraffin-embedded tissue sections from 16 FAs, 12 MICs, and 4 EICs were studied for immunohistochemical expression of CR and CD. Percent of tumor staining, intensity of staining, and intracytoplasmic staining pattern were assessed. Increased intensity of staining with CD was observed in follicular carcinomas compared to adenomas and was greatest in the EIC (p < 0.04). An increase in diffuse cytoplasmic staining pattern with CD (p < 0.008) and CB (p < 0.02) was observed in follicular carcinomas compared to FAs. The increased intensity of staining with CD in the follicular thyroid carcinomas and the increased diffuse cytoplasmic staining pattern with CD and CR in these carcinomas suggest that these proteinases may play a role in their propensity to invade and metastasize and, therefore, their more aggressive behavior. Furthermore, this diffuse cytoplasmic staining suggests an altered intracellular processing of these proteinases in the carcinomas.
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PMID:Cathepsin B and Cathepsin D Expression in Follicular Adenomas and Carcinomas of the Thyroid Gland. 1211 71

Pituitary carcinomas are only defined by their metastatic growth, which may be intracranial or systemic. To establish further morphological and immunohistochemical differences between pituitary carcinomas and adenomas, 19 ACTH-secreting adenomas (10 non invasive and 9 invasive) and 2 ACTH-secreting carcinomas with their metastases were studied for expression of the intermediate filaments keratin and vimentin and the tumor-associated antigens Ki67, proliferating cell nuclear antigen (PCNA), epidermal growth factor (EGF), cathepsin D, p53, and carcinoembryonic antigen (CEA). Immunohistochemistry was performed using avidin-biotin techniques on formalin-fixed, paraffin-embedded tissue. With the exception of one noninvasive pituitary adenoma, one carcinoma, and the metastases, all tumors contained keratin; none contained vimentin. All tumors stained negative for CEA and p53. Eleven (58.5%) adenomas and both pituitary carcinomas contained Ki67-positive nuclei; 14 (74%) adenomas and one carcinoma revealed PCNA. No correlation was found between the two markers. Seven (38%) adenomas showed a labeling index <1 % for cathepsin D, whereas none of the carcinomas or metastases did so. EGF was found in 7 (38%) adenomas and in both carcinomas. A tendency to a higher rate of EGF positivity in the invasive adenomas was observed. The metastases showed a higher labeling index, and far more intense staining results for Ki67, PCNA, and EGF than the primary tumor. The metastases also had a higher proliferation rate and growth factor content than the carcinoma itself.
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PMID:Proliferation Markers and EGF in ACTH-Secreting Adenomas and Carcinomas of the Pituitary. 1211 89

Cathepsin D is a lysosomal acid proteinase which is involved in the malignant progression of breast cancer and other gynecological tumors. Clinical investigations have shown that in breast cancer patients cathepsin D overexpression was significantly correlated with a shorter free-time disease and overall survival, whereas in patients with ovarian or endometrial cancer this phenomenon was associated with tumor aggressiveness and a degree of chemoresistance to various antitumor drugs such as anthracyclines, cis-platinum and vinca alkaloids. Therefore, a lot of research has been undertaken to evaluate the role and the prognostic value of cathepsin D also in other solid neoplasms. However, conflicting results have been generated from these studies. The discrepancies in these results may, in part, be explained with the different methodological approaches used in order to determine the levels of expression of the enzyme in tumor tissues and body fluids. Further investigations using well-standardized techniques may better define the clinical significance of cathepsin D expression in solid tumors. Nevertheless, evidence emerging from these studied indicates that this proteinase seems to facilitate early phases of tumor progression such as cell proliferation and local dissemination. These findings support the concept that cathepsin D may be a useful marker for identifying patients with highly malignant tumor phenotypes who may need more aggressive clinical treatment; this enzyme may also be considered as a potential target for a novel therapeutic approach in the treatment of solid neoplasms.
Clin Exp Metastasis 2004
PMID:Cathepsin D expression levels in nongynecological solid tumors: clinical and therapeutic implications. 1516 27

In the process of metastasis, malignant cells are released from the primary tumor and migrate to specific organs via the lymphatic and blood circulation systems. These circulating tumor cells have been characterized by immunochemistry, the reverse transcription-polymerase chain reaction, and flow cytometry. Using the MCF-7 breast cancer cell line, we have developed a two-color ELISPOT assay to detect cells secreting cathepsin D protease and MUC1 glycoprotein, markers associated with the risk of metastases in breast cancer. The threshold of detection of this ELISPOT assay was one cathepsin D- or MUC1-secreting MCF7 cell per 5 ml of control blood. In 16 patients with breast carcinoma metastases, 1 to 1940 cathepsin D- or MUC1-secreting cells per 2x10(7) PBMC were enumerated, whereas none were found in 11 controls. Moreover, in six patients 6-60% of MUC1-secreting cells also expressed the CXCR4 chemokine receptor, which is involved in the homing of metastatic breast cancer cells. The ELISPOT assay described here allowed us to enumerate cathepsin D- and/or MUC1-secreting cells in the MCF-7 cell line and in the peripheral blood of patients with disseminated breast cancer. The combination of the ELISPOT assay and CXCR4-positive cell sorting identified subsets of MUC1-secreting cells in the peripheral blood of these patients.
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PMID:Characterization and enumeration of cells secreting tumor markers in the peripheral blood of breast cancer patients. 1591

In order to address the heterogeneity of the pT1 breast cancer stages, we have been examining the natural and the clinical course of disease in relation to cathepsin D expression, as a molecular marker for the tumor progression that leads to metastasis. The original aim of our pilot study was to determine whether it was possible to distinguish high-risk from low-risk patients, on the basis of nonestrogen- vs. estrogen-regulated cathepsin D expression. Our results showed that estrogen-regulated cathepsin D expression could be useful as surrogate marker of node-positive status. Further, during the natural course of disease, none of 7 pT1N0 patients with tumors bearing nonestrogen-regulated cathepsin D expression developed metastasis. During the clinical course of disease, nonestrogen-regulated cathepsin D expression defined low-risk while estrogen-regulated cathepsin D expression defined high-risk pT1N+ subgroup of patients. Although there is no consensus with respect to metastasis-related prognostic value of cathepsin D expression, our pilot study implies its prognostic value in pT1 breast cancer patients and supports the hypothesis that cathepsin D may promote metastasis in this early stage of disease.
Clin Exp Metastasis 2005
PMID:Cathepsin D-related disease-free interval in pT1 primary breast carcinomas: a pilot study. 1617 Jun 72


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