Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD63 belongs to the transmembrane 4 superfamily of membrane proteins and is expressed in several normal tissues as well as in melanoma cells. Previous reports have suggested that CD63 may play an important role in inhibiting melanoma progression, and this was supported by our studies showing that CD63 was associated with suppression of the growth of melanoma in nude mice. Recently, we and others have shown that CD63 may form noncovalent associations with beta1 integrins, which suggests that the function of CD63 may be related to that of integrins. To further explore the role of CD63 in melanoma, we transfected CD63 into a highly motile, CD63-negative melanoma cell line, KM3, which was shown to express alpha(v)beta5 as the predominant integrin with only trace amounts of beta1 integrins. Following transfection, CD63 was shown to associate with beta1 integrins, and beta1 expression appeared to be up-regulated. Cell motility in serum-containing media was markedly suppressed following transfection of CD63. This inhibition was potentiated by mAbs to CD63, and correlated with the level of CD63 expression. The CD63-transfected, but not the untransfected, melanoma cells showed increased adhesion and migration on the beta1 substrates, fibronectin, laminin, and collagen, whereas rates of migration were similar on the beta5 substrate, vitronectin. These results show that CD63 is involved in regulation of the motility of melanoma cells and their adhesion and migration on substrates associated with beta1 integrins. We suggest they provide further insights into the role of CD63 in tumor progression.
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PMID:Regulation of tumor cell motility and migration by CD63 in a human melanoma cell line. 912 Feb 93

We have developed a novel murine mammary tumor system with variants representing different stages of tumor progression. The MXT-s parental cell line was established from a urethane-induced and hormone-sensitive mammary tumor. MXT-s parental cells are highly tumorigenic but poorly metastatic. MXT clones and variants were selected by either in vitro or in vivo procedures, and they differ in metastatic ability and 17 beta-estradiol dependency for tumor growth. The MXT-c1.1 and MXT-B2 cell lines produced lung metastasis after intravenous injection into 100% of syngenic mice, but only MXT-c1.1 cells were highly metastatic from intramammary tumors. The fingerprints obtained by arbitrarily primed-polymerase chain reaction demonstrated that the metastatic variants and clones had a common genetic background and resulted from clonal selection from the parental cell line. We studied whether the matrix metalloproteinase (MMP) profile is correlated with tumor progression and metastatic ability in the MXT tumor system. Gelatinases A and B were assayed in the cells, both by enzyme activity and mRNA expression. Gelatinase A was expressed in MXT-c1.1 cells, whereas MXT-B2 cells did not express either MMP. In contrast, the mammary fat pad tumors expressed both gelatinases. Membrane Type 1-MMP transcripts were also detected in MXT cells and tumors. Because the mRNA levels of gelatinase. A were low in MXT-B2 tumors, we suggested that exogenous gelatinase A bound the cell membranes of MXT-B2 cells in vivo. Indirect evidence was obtained in vitro by treatment of MXT-B2 cells with NIH/3T3 fibroblast-conditioned medium. After this treatment, we detected a gelatinolytic activity at M(r) 68,000 in the cell-membrane extract of MXT-B2 cells and an increase in migratory ability through type IV collagen matrices. On the other hand, Ha-ras gene dosage correlated positively with metastatic ability but not with either gelatinase A or gelatinase B expression. No significant differences were observed in the expression of stromelysin-1 and tissue inhibitors of MMP. Thus, in the MXT tumor system, the expression of gelatinase A or its cell association and Ha-ras gene dosage independently contribute to the metastatic phenotype.
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PMID:Metastatic ability of MXT mouse mammary subpopulations correlates with clonal expression and/or membrane-association of gelatinase A. 918 Sep 29

By the degradative effect on basement membrane collagen type IV, matrix metalloproteinases (MMPs) or gelatinases are important in the early invasion of malignant tumors. These enzymes may be released by the tumor cells themselves or may be derived from nearby fibroblasts that have been stimulated by the extracellular MMP inducer EMMPRIN. We studied the distribution of 92-kd gelatinase B (MMP-9) and of EMMPRIN in 33 benign and 41 malignant, paraffin-embedded pigment cell lesions using immunohistochemistry and monoclonal antibodies. In benign pigment cell lesions, EMMPRIN but not gelatinase B was expressed in cellular blue nevi whereas all other benign lesions, including common blue nevi, were negative. In malignant melanomas (MMs), both gelatinase B and EMMPRIN were variably expressed in the pure and invasive radial growth phase but not in the vertical growth phase. All lentigo maligna cases and all metastatic lesions were negative. Of MMs with thickness < 1.6 mm, 63% expressed gelatinase B and 70% expressed EMMPRIN, whereas in MMs with > 1.6 mm thickness, only 10% expressed gelatinase B and only 25% expressed EMMPRIN. We conclude that early invasion of MM is associated with de novo expression of gelatinase B and EMMPRIN by neoplastic melanocytes. Expression of EMMPRIN and MMP-9 may be partly responsible for the stromal changes observed in thin MM. Their absence in the vertical growth phase and in metastatic lesions suggests that other factors are involved in tissue degradation during later stages of tumor progression in MM. The lack of both gelatinase B and EMMPRIN in lentigo maligna may contribute to the indolent behavior of this type of pigment cell lesion.
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PMID:Expression of gelatinase B and the extracellular matrix metalloproteinase inducer EMMPRIN in benign and malignant pigment cell lesions of the skin. 928 14

The deterioration of extracellular matrix turnover is a key event in tumor progression. It has been assumed that Ito cell transformation is stimulated by tumor-derived factors. In the present study changes in the occurrence of collagen type III and IV and Ito cell transformation are described in the sinusoids of patients with malignant gastrointestinal tumors without liver metastases, and around metastatic liver tumors using routine histology, electron microscopy as well as light microscopical and ultrastructural immunohistochemistry. Dilated sinusoids filled with lymphoid cells and variable perisinusoidal fibrosis were detected light microscopically. Collagen type III and IV immune deposits were increased perisinusoidally. Ultrastructural immunohistochemistry showed increased staining in the space of Disse and around Ito and transitional cells for both types of collagen. Ito cells were transformed into transitional cells. Pit cells appeared in the inflammatory infiltrate in sinusoids. Ito cells were significantly increased in number pericentrally and periportally. It is suggested that stimuli, which can influence Ito cellular behaviour are produced by inflammatory cells in sinusoids, resident sinusoidal cells, tumor cells or by tumor stroma. It is concluded that transformed Ito cells and increased amounts of collagen type III and IV in sinusoids of patients with malignant tumors without liver metastases or around metastatic tumors may predict tumor-related alterations of liver parenchyma, which may serve as a barrier for further outgrowths of the cancer cells.
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PMID:Carcinoma-associated collagen type III and type IV immune localization and Ito cell transformation indicate tumor-related changes in sinusoids of the human liver. 938 15

The extracellular matrix (ECM) is known to play an active role in numerous biological processes such as differentiation, apoptosis and cancer. Extensive alterations of epithelial basement membranes and of interstitial ECM are known to occur during the progression of most invasive carcinomas. Collagen, which represents the major component of the interstitial ECM, is primarily involved in the stromal changes at the site of tumor cell invasion. We have previously described the occurrence in breast and colon cancer ECM of an oncofetal form of collagen, characterized by an acidic chain distinct from those of type I and III collagen. In the present paper, we bring evidence that alpha2(I) collagen chains in colon cancer tissues expressing the acidic chains, are either overmodified or absent, both as protein and as regular mRNA transcripts. The results obtained strongly suggest that: i) the disorganisation of the collagen architecture and the phenomenon of fibril dispersion, which accompanies the lysis of basement membrane, is not only due to the enzymatic degradation of the collagen fibres, but presumably also to changes of the collagen molecules deposited in the stroma; ii) the neosynthesis of collagen occurring at tumor-host interface is deeply deregulated, and therefore to be considered the result of altered collagen gene expression correlated with the tumor progression, rather than as a mere defensive reaction of the host cells.
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PMID:Absence of regular alpha2(I) collagen chains in colon carcinoma biopsy fragments. 960 Mar 40

CD44, a major hyaluronan receptor, exists as several isoforms and is widely distributed in different cells and tissues. The isoforms of CD44, such as CD44s (the standard form), CD44E (the epithelial form) and CD44v (variant isoforms) (arise from differential splicing of one to ten (or eleven) variable exons that encode portions of the membrane proximal extracellular domain. The molecular diversity of CD44 isoforms is further compounded by differential biosynthetic processes and post-translational modifications [e.g. N-/O-glycosylation or glycosaminoglycan (GAG) addition]. This structural arrangement, which occurs within either the invariant region or the extracellular domain of the variant region, is important for CD44-mediated communication between extracellular matrix materials [ECM-hyaluronic acid (HA), collagen and fibronectin] and intracellular protein components (e.g cytoskeletal proteins and various regulatory enzymes). The 15 amino acid sequence [e.g. NSGNGAVEDRKPSGL (in human) or NGGNGTVEDRKPSEL (in mouse)] residing in the cytoplasmic domain of CD44 isoforms is the ankyrin-binding domain of this family of transmembrane glycoproteins. Biochemical analyses plus in vitro mutagenesis indicate that the ankyrin-binding domain is required for CD44-mediated "outside-in" and "inside-out" cell activation events. Furthermore, CD44s-cytoskeleton interaction is tightly coupled with signal transducing molecules (e.g. p185HER2 or Src kinases) during oncogenic signaling. Moreover, the transmembrane linkage between CD44v isoforms (CD44v10 and CD44v3) and the cytoskeleton up-regulates invasive and metastatic-specific tumor phenotypes [e.g. matrix degradation (MMPs) activities, tumor cell invasion and migration]. These findings strongly suggest that the interaction between CD44 isoforms and the cytoskeleton plays a pivotal role in the onset of oncogenesis and tumor progression.
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PMID:CD44 isoform-cytoskeleton interaction in oncogenic signaling and tumor progression. 963 39

The secretion of specific matrix metalloproteinases (MMPs) is considered a prerequisite step for tumor cell invasion and metastasis. In the present study we investigated the expression of type IV collagen-degrading activity in primary tumors of the human colon in correlation to tumor grade and in comparison to activity expressed in arising metastases. We observed that type IV collagen-degrading activity (MMP-2 and MMP-9), purified by ion exchange, gel filtration and affinity chromatography and characterized by gelatin zymography, correlates to tumor grade. Furthermore, in surgical specimens identified as metastases originating from primary tumors of the colon, we observed that enzyme activity was significantly enhanced, relatively to that identified in the primary tumor. This observation should be considered when targeting MMPs as a therapeutic intervention to prevent cancer progression.
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PMID:Increased type IV collagen-degrading activity in metastases originating from primary tumors of the human colon. 970 42

Various growth factors and basement membrane proteins have been implicated in the pathobiology of astrocytomas. The goal of this study was to determine the relative contribution of these two factors in modulating the phenotype of U-373 MG glioblastoma cells as determined by the expression of the intermediate filament proteins glial fibrillary acidic protein, vimentin, and nestin. For these determinations, cells plated in serum-free medium were treated either with growth factors binding to tyrosine kinase receptors including transforming growth factor-alpha, epidermal growth factor, platelet-derived growth factor-AA, basic fibroblast growth factor, and insulin-like growth factor-1 or with basement membrane proteins including collagen IV, laminin, and fibronectin. The changes in the expression levels of intermediate filament proteins in response to these treatments were analyzed by quantitation of immunoblots. The results demonstrate that collagen IV and growth factors binding to tyrosine kinase receptors decrease the glial fibrillary acidic protein content of U-373 MG cells. Growth factors binding to tyrosine kinase receptors also decrease the vimentin content of these cells but do not affect their nestin content. On the other hand, basement membrane proteins decrease the nestin content of U-373 MG cells but do not affect their vimentin content. The significance of these results with respect to the role played by different factors in modulating the phenotype of neoplastic astrocytes during tumor progression is discussed.
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PMID:Effects of growth factors and basement membrane proteins on the phenotype of U-373 MG glioblastoma cells as determined by the expression of intermediate filament proteins. 977 47

The importance of tumor-stroma interaction in many solid tumors of the skin has been demonstrated in recent years. Invasion and metastasis require multiple interactions of the tumor cells with the surrounding stroma. In malignant melanoma most studies concerning tumor-stroma interaction focus on the peritumoral infiltrate, whereas other aspects of tumor-stroma interactions have not been considered. We investigated two morphologic criteria of tumor-stroma interaction in melanocytic skin tumors. Simple infiltration into the surrounding dermis or subcutis without evident stromal reaction (DERMSIMPLE) and the existence of morphologically intact collagen bundles of the reticular dermis within the tumor bulk (PRECOLL) were examined in 373 benign common nevi, 239 dysplastic nevi, 322 Spitz nevi, 368 primary malignant melanomas, and 344 melanoma lesions metastatic to the skin. Our results showed that there is a highly significant difference in the expression of DERMSIMPLE and PRECOLL between benign and malignant melanocytic skin tumors. Concerning DERMSIMPLE, 13.3% of benign skin lesions compared with 28.2% of malignant lesions were positive for this feature; PRECOLL was found in 13.8% benign and 37.1% malignant lesions (chi-squared test; p = 0.0001 for both features). Furthermore, it could be demonstrated that simple infiltration into the surrounding stroma as well as the existence of morphologically intact collagen bundles of the reticular dermis within the tumor bulk increases with tumor progression; between primary malignant melanoma and melanoma metastatic to the skin, for example, there was a highly significant difference for DERMSIMPLE, as well as for PRECOLL (chi-squared test; p = 0.00001). These data indicate that morphologic aspects of tumor-stroma interactions in different benign and malignant melanocytic skin lesions may reflect biological behavior of tumor cells. The analysis of further aspects of tumor-stroma interaction and the relation to the patient's outcome may lead to the development of further prognostic parameters in malignant melanoma.
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PMID:Expression of two morphologic parameters concerning tumor-stroma interaction in benign and malignant melanocytic skin lesions. 979 Jan 7

A case of an aggressive desmoid tumor in a patient with familial adenomatous polyposis is described. The lesion rapidlyenlarged with compression of adjacent structures including the ureter and small bowel, and the patient died because of small bowel perforation and hydronephrosis 3 years after detection of small desmoid tumors at the time of a prophylactic coloproctectomy for a colon carcinoma. Immunohistochemically, proliferating cell nuclear antigen (PCNA), p21WAF1/CIP1 and cathepsin D indices, but not the bcl-2 index, which were defined as the numbers of immunoreactive tumor cells per 1000 tumor cells, increased in line with tumor progression. The tumor did not show staining for collagen IV, but was characterized by intense staining for basic fibroblast growth factor (bFGF). Accordingly, tumor aggression was related to increases in both cell proliferation and protease activity, as well as an enhanced expression of bFGF. In addition, the desmoid tumor showed deregulation between PCNA and p21WAF1/CIP1 because the normal inverse relation between these two was not apparent.
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PMID:An aggressive desmoid tumor in a patient with familial adenomatous polyposis: immunohistochemical findings. 1002 64


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