Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the extravasation and subsequent migration and growth of murine mammary tumor cell lines (D2A1 and D2.OR) which differ in their metastatic ability in lung and liver, invasiveness in vitro and expression of the cysteine proteinase cathepsin L. In light of the differences in invasiveness and cathepsin L expression, we hypothesized that during hematogenous metastasis the two cell lines would differ primarily in their ability to extravasate. We used in vivo videomicroscopy of mouse liver and chick embryo chorioallantoic membrane to examine the process and timing of extravasation and subsequent steps in metastasis for these cell lines. In contrast to our expectations, no differences were found between the cell lines in either the timing or mechanism of extravasation, at least 95% of cells having extravasated by 3 days after injection. However, after extravasation, the more metastatic and invasive D2A1 cells showed a greater ability to migrate to sites which favor tumor growth and to replicate to form micrometastases. These studies point to post-extravasation events (migration and growth) as being critical in metastasis formation.
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PMID:Mammary carcinoma cell lines of high and low metastatic potential differ not in extravasation but in subsequent migration and growth. 792 88

SCC antigen is a tumor-associated protein of squamous cell carcinoma of various organs. So far, two genes (SCC Ag-1 and SCC Ag-2) have been identified, and their products are highly homologous and classified as serine protease inhibitors (serpin). Recombinant SCC antigen-1 inhibits chymotrypsin and cathepsin L in vitro, indicating that it is inhibitory type serpin. Transduction of tumor cells with SCC antigen-1 reveals that SCC antigen-1 inhibits apoptosis of tumor cells induced by anticancer drug, TNFalpha or NK cells. Therefore SCC antigen-1 may work in cancer cells for tumor growth, and in normal squamous epithelium for differentiation by means of the inhibition of apoptosis. Recombinant SCC antigen-2 inhibits cathepsin G and mast cell chymase, suggesting that it protects epithelial cells from the inflammation induced by these proteases.
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PMID:Biological role of SCC antigen. 981 78

The influence of Ukrain (exerting a malignotoxic effect in vivo according to Nowicky J.W. et al [1]) on the growth of Hepatoma A (HA-1) tumors in mice and cysteine proteinases as markers of tumor growth and malignancy was studied. Ukrain administration (0.5 mg per mice of 20 g, in each of 5 i.p. injections) resulted in a reproducible and significant retardation of HA-1 tumor growth in the liver and a prolongation of lifespan compared with the untreated control. Repeated Ukrain administration to mice increased the number of macrophages in ascites, decreased the number of tumor cells, and concomitantly reduced the increased level of monocytes in peripheral blood. In ascitic cells the specific activity of cathepsin B was higher than in the intact liver and was not influenced by Ukrain; activity of cysteine proteinases studied in ascitic fluid was much higher than that in serum. Tumor growth was followed by a decrease in cathepsin B activity in the liver and serum at day 10. Ukrain administration has a tendency to normalize the disturbances of cathepsin B activity during tumor development. The cathepsin L activity changes in ascitic fluid were more impressive than those of cathepsin B, indicating the special role of this cysteine proteinase in HA-1 tumor growth and invasiveness. The role of cysteine proteinases as markers of tumor malignancy and invasiveness is discussed.
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PMID:The influence of Ukrain on the growth of HA-1 tumor in mice: the role of cysteine proteinases as markers of tumor malignancy. 1019 85

Endostatin, an inhibitor of angiogenesis and tumor growth, was identified originally in conditioned media of murine hemangioendothelioma (EOMA) cells. N-terminal amino acid sequencing demonstrated that it corresponds to a fragment of basement membrane collagen XVIII. Here we report that cathepsin L is secreted by EOMA cells and is responsible for the generation of endostatin with the predicted N-terminus, while metalloproteases produce larger fragments in a parallel processing pathway. Efficient endostatin generation requires a moderately acidic pH similar to the pericellular milieu of tumors. The secretion of cathepsin L by a tumor cell line of endothelial origin suggests that this cathepsin may play a role in angiogenesis. We propose that cleavage within collagen XVIII's protease-sensitive region evolved to regulate excessive proteolysis in conditions of induced angiogenesis.
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PMID:Secreted cathepsin L generates endostatin from collagen XVIII. 1071 19

The aim of this study was to evaluate the histopathologic features and the expression of angiogenesis-related markers in primary tumors and metastatic lymph nodes of oral squamous cell carcinomas (SCCs) with multiple lymph node involvement in comparison with oral SCCs without nodal metastasis. The protein levels of the angiogenesis inhibitor endostatin, as well as those of the related molecules collagen XVIII, collagen-binding protein (CBP) 2/heat shock protein (HSP) 47, and cathepsin L, were evaluated by immunohistochemical analysis. Compared with nonmetastatic cases, primary tumors of the metastatic group exhibited significantly decreased protein levels of endostatin and its precursor collagen XVIII. Comparison between primary tumors and positive nodes of the metastatic cases revealed decreased expression of collagen XVIII and CBP2/HSP47 in metastases. Angiogenesis is essential for tumor growth and metastasis; accordingly, the observed differences in the immunohistochemical expression of angiogenesis-related proteins in oral SCC with multiple lymph node involvement may provide an explanation for the increased metastatic potential of these tumors.
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PMID:Immunohistochemical expression of angiogenesis-related markers in oral squamous cell carcinomas with multiple metastatic lymph nodes. 1271 Jan 30

We demonstrated previously that the switch from nonmetastatic to highly metastatic phenotype of human melanoma cells is directly related to secretion of procathepsin L form. This cysteine proteinase was identified on the basis of its property to cleave human C3, the third component of complement. In an attempt to control procathepsin L secretion, we have recently generated an anti-cathepsin L single chain variable fragment (ScFv) from an anti-cathepsin L monoclonal antibody generated against recombinant cathepsin L. We herein selected clones stably transfected with this anti-cathepsin L ScFv and analyzed them for changes in tumor growth and metastasis. We show that in stably transfected clones, anti-cathepsin L ScFv strongly inhibited the secretion of procathepsin L without modifying the intracellular amount or processing pattern of cathepsin L forms. Confocal analysis demonstrated colocalization of endogenous cathepsin L and anti-cathepsin L ScFv. In addition, expression of this ScFv strongly inhibited generation of tumor and metastasis by these human melanoma clones in nude mice. In vivo, the anti-cathepsin L ScFv-transfected cells produced tumors with decreased vascularization (angiogenesis) concomitant with increased apoptosis of tumor cells. Matrigel assay also demonstrated that melanoma invasiveness was completely abolished. Thus, this is the first demonstration that anti-cathepsin L ScFv could be used to inhibit the tumorigenic and metastatic phenotype of human melanoma, depending on procathepsin L secretion, and could therefore be used as a molecular tool in a therapeutic cellular approach.
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PMID:Inhibition of tumorigenicity and metastasis of human melanoma cells by anti-cathepsin L single chain variable fragment. 1472 18

Cathepsins are papain-like lysosome cysteine proteases involved in tumor growth, invasiveness and spread, angiogenesis and alteration in immune and inflammatory responses. We investigated the differences in cathepsin L (CatL) concentrations in primary cutaneous malignant melanoma stage I and normal skin and correlated these values with well-established malignant melanoma prognostic factors. The study was performed on 36 patients (17 men and 19 women; mean age 54 years; range 21-84 years) with histological confirmed primary malignant melanomas less than 1.5 mm thick. The CatL concentrations were measured in 36 pairs of triton extracts of cytosols prepared from the tumor and adjacent normal tissue samples (matched pairs). The CatL concentrations were determined by commercially available enzyme-liked immunosorbent (ELISA) assay from KRKA (Novo Mesto, Slovenia). Significantly higher concentrations of CatL were detected in malignant melanomas than in normal surrounding skin (6.73 vs. 1.42 ng/mg total protein (mgp), p<0.001). Significant correlations between malignant melanoma and normal skin concentrations for CatL were found. The malignant melanoma CatL concentrations correlated significantly with normal skin (r=0.38; p=0.021). CatL concentrations were significantly lower (p<0.01) in the malignant melanomas of Breslow thickness <or=0.75 mm, Clark invasion <II, without microscopic ulceration and without vascular invasion (4.14, 4.73, 6.15, 5.29 ng/mgp, respectively) than in the malignant melanomas of Breslow thickness >0.75 mm, Clark invasion of >or=II and <or=III, with microscopic ulceration and with vascular invasion (7.67, 7.41, 9.15, 10.35 ng/mgp, respectively). Higher CatL concentrations in early primary malignant melanomas indicate its possible involvement in the processes of early metastatic spread and its association with poor prognosis.
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PMID:Expression and prognostic significance of Cathepsin L in early cutaneous malignant melanoma. 1665 98

The cleaved approximately 22-kDa form of Endothelial-Monocyte Activating Polypeptide [mature (m)EMAP II] functions as a potent inhibitor of tumor growth. Although the anti-tumor effect of mEMAP II has been described, little is known regarding the cleavage of mEMAP II from its precursor form (pEMAP II). We determined that pEMAP II is expressed at the cell membrane surface and proteinases MMP-9, elastase, and cathepsin L release protein fragments consistent with mEMAP II molecular mass. MMP-9 and elastase generate a approximately 25-26 kDa spanning fragments, while cathepsin L generates a approximately 22 kDa fragment. Although several fragments are processed from pEMAP II within a 44 AA residue stretch, cathepsin L cleaves pEMAP II within 4 amino acids of the determined N-terminal sequence, suggesting that this region is sensitive to proteinases.
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PMID:Identification of protease-sensitive sites in Human Endothelial-Monocyte Activating Polypeptide II protein. 1667 41

CML66 is a novel, promising tumor antigen; however, its biological roles remain unclear. In present study, we applied a short hairpin RNA triggered RNA interfering to suppress CML66 expression in HeLa cervical carcinoma cells. Knockdown of CML66 inhibited proliferation, migration and invasion activities of HeLa cells in vitro. Meanwhile, in nude mice, CML66 silencing suppressed tumor growth and pulmonary metastasis with HeLa cells injected subcutaneously. Furthermore, using metastasis-related genes cDNA microarrays, we found 9 genes were significantly down-regulated after CML66 silencing, including cathepsin L, MMP15, uPAR, VEGF, COX-2, S100A4, MUC1, MDM2 and RAC1. These results imply that CML66 may play an oncogenic role in ways of favoring tumor cells proliferation, invasion and metastasis-associated with multiple pathways. Thus, CML66 might be a potential target for development of cancer therapy.
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PMID:RNA interference targeting CML66, a novel tumor antigen, inhibits proliferation, invasion and metastasis of HeLa cells. 1853 45

We previously demonstrated that the switch from non- to highly tumorigenic phenotype of human melanoma cells is directly related to procathepsin L secretion, which increased cell resistance to complement-mediated cell lysis. Involvement of procathepsin L secretion in tumor growth was clearly demonstrated by three different strategies: (1) inhibition of secreted procathepsin L activity; (2) increase of procathepsin L secretion; and (3) inhibition of procathepsin L secretion. This latter strategy was triggered by intracellular expression of anti-human cathepsin L single-chain variable fragment (ScFv). These previous experiments were performed by processing melanoma cells before their injection into nude mice. We herein designed a new lentiviral vector in which this anti-cathepsin L ScFv was cloned. This lentiviral vector was optimized to allow the highest intracellular expression of anti-cathepsin L ScFv in transduced melanoma cells. In these transduced cells, procathepsin L secretion was strongly inhibited. In addition, injection of this anti-cathepsin L ScFv lentiviral vector into tumors already induced in nude mice inhibited tumor growth and associated angiogenesis. This is the first report to demonstrate that targeting procathepsin L secretion with anti-cathepsin L ScFv lentiviral construct constitutes a new gene therapy in the challenge to inhibit the growth of tumors induced by human melanoma cells.
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PMID:Intratumoral gene delivery of anti-cathepsin L single-chain variable fragment by lentiviral vector inhibits tumor progression induced by human melanoma cells. 1861 16


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