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

Glypican-3 (GPC3), a proteoglycan bound to the cell membrane through a GPI anchor, is widely expressed in the embryo but down regulated in most adult tissues, with some exceptions as mammary cells. GPC3 is involved in the regulation of cell proliferation and survival in specific cell types. LM3, a murine mammary tumor cell line unable to express GPC3, was stably transfected with the rat GPC3 gene to analyze its role in tumor progression. Upon injection into syngeneic BALB/c mice LM3-GPC3 clones showed less local invasiveness and developed fewer spontaneous and experimental lung metastasis than controls. GPC3-expressing cells were more sensitive to apoptosis induced by serum depletion, exhibited a delay in the first steps of spreading and were less motile than controls. On the other hand, LM3-GPC3 cells were significantly more adherent to FN than control ones. We observed that GPC3 transfectants presented a higher expression of E-cadherin and beta-catenin, molecules whose down regulation has been associated with tumor progression. Exogenous TGF-beta increased MMP-9 activity in both control and GPC3-expressing cells, but did not modulate MMP-2. Contrarily, GPC3 expression prevented the increase of MMP-2 activity induced by IGF-II. Our results suggest that GPC3 has a protective role against mammary cancer progression.
 ...
PMID:Inhibition of invasion and metastasis by glypican-3 in a syngeneic breast cancer model. 1290 26

Tenascin and decorin are components of the extracellular matrix (ECM) that are implicated in cell proliferation in tumors. Here, we propose that abnormal expression of stromal ECM may play an important role in the progression of intrahepatic cholangiocarcinoma, which is characterized by desmoplastic reaction. To explore this hypothesis, we performed immunohistochemical analysis in order to examine the expression and distribution of tenascin and decorin in 75 cases of intrahepatic cholangiocarcinoma. In the intratumoral stroma, positive staining for tenascin was observed in 51 (68%) cases, and positive staining for decorin was observed in 61 (81%) cases. However, at the invasive front, positive staining for tenascin was found in 23 (31%) cases, and positive staining for decorin was found in 6 (8%) cases. Decorin staining was not correlated with aggressive behavior of intrahepatic cholangiocarcinoma, whereas intratumoral tenascin staining was correlated with lymphatic permeation and proliferative activity measured by Ki67. Tenascin staining at the invasive front was associated with tumor size, lymphatic permeation, lymph node metastasis, and proliferative activity and appeared to be a useful prognostic factor by univariate analysis, although it was not an independent prognostic factor. These results indicate that tenascin plays a role in tumor progression in cases of intrahepatic cholangiocarcinoma and that tenascin expression, especially at the invasive front, may be a useful marker in evaluating an unfavorable prognosis in patients with intrahepatic cholangiocarcinoma.
 ...
PMID:Tenascin expression at the invasive front is associated with poor prognosis in intrahepatic cholangiocarcinoma. 1455 85

Angiogenesis, the process of new capillary formation from pre-existing vessels, has been established as an important mechanism involved in pathologic processes, such as cancer, as well as in normal physiology (Ribatti, D.; Vacca, A.; Roncali, L.; Dammacco, F. Angiogenesis under normal and pathological conditions. Haematologica 1991, 76 (4), 311-320). Basic fibroblast growth factor (FGF-2) is a critical mediator of angiogenesis that is important for normal reproduction and wound healing. FGF-2 mediates its pro-angiogenic effects by binding to heparin sulfate proteoglycan in addition to a tyrosine kinase receptor (Baird, A.; Schubert, D.; Ling, N.; Guillemin, R. Receptor and heparin-binding domain of basic fibroblast growth factor. Proc. Natl. Acad. Sci. U. S. A. 1998, 5 (7), 2324-2328; Richard, C.; Roghani, M.; Moscatelli, D. Fibroblast growth factor (FGF)-2 mediates cell attachment through interactions with two FGF receptor-1 isoforms and extracellular matrix or cell-associated heparin sulfate proteoglycans. Biochem. Biophys. Res. Commun. 2000, 276 (2), 399-405; Casu, B.; Guerrini, M.; Naggi, A.; Perez, M.; Torri, G.; Ribatti, D.; Carminati, P.; Giannini, G.; Penco, S.; Pisano, C.; Belleri, M.; Rusnati, M.; Presta, M. Short heparin sequences spaced by glycol-split urinate residues are antagonists of fibroblast growth factor 2 and angiogenesis inhibitors. Biochemistry 2002, 41 (33), 10519-10528; Murphy, P.V.; Pitt, N.; O'Brien, A.; Enright, P.M.; Dunne, A.; Wilson, S.J.; Duane, R.M.; O'Boyle, K.M. Identification of novel inhibitors of fibroblast growth factor (FGF-2) binding to heparin and endothelial cell survival from a structurally diverse carbohybrid library. Bioorg. Med. Chem. Lett. 2002, 12 (22), 3287-3290). We developed a liposomal-based peptide vaccine, L(HBD) that targets the heparin binding domain of the FGF-2 molecule. This vaccine, when inoculated into mice, inhibits angiogenesis in response to FGF-2 in a hepatic sponge model as well as tumor progression in two models of pulmonary metastatic disease. In the present studies, we further characterize the immunological and physiological responses to this vaccine. Vaccinated animals generated a specific anti-FGF-2 antibody (titer of 1:5000) that was able to inhibit FGF-2 binding to heparin sulfate in a dose dependent fashion. Cell mediated immunity was evidenced by a delayed type hypersensitivity response following challenge with the heparin binding domain peptide. Despite an immune response toward FGF-2, vaccination with L(HBD) did not result in alterations in mean time to wound healing when compared to unvaccinated animals or those treated with a liposome control. In reproductive studies, vaccinated females were not impaired in their ability to: 1) become pregnant, 2) support the growth and development of their embryos, and 3) deliver viable offspring. Furthermore, when assessed histologically, these offspring did not demonstrate any alterations in organogenesis when compared to pups born to untreated or liposome control treated females. Thus, while vaccination against FGF-2 induces a specific FGF-2 antibody response, and inhibits angiogenesis and tumor development in a pathological setting, it does not adversely alter normal physiological events dependent on FGF-2.
 ...
PMID:Generation of a specific immunological response to FGF-2 does not affect wound healing or reproduction. 1510 30

CD97, a membrane protein expressed at high levels on inflammatory cells and some carcinomas, is a member of the adhesion G protein-coupled receptor family, whose members have bipartite structures consisting of an extracellular peptide containing adhesion motifs noncovalently coupled to a class B 7-transmembrane domain. CD97alpha, the extracellular domain of CD97, contains 3 to 5 fibrillin class 1 epidermal growth factor (EGF)-like repeats, an Arg-Gly-Asp (RGD) tripeptide, and a mucin stalk. We show here that CD97alpha promotes angiogenesis in vivo as demonstrated with purified protein in a directed in vivo angiogenesis assay (DIVAA) and by enhanced vascularization of developing tumors expressing CD97. These data suggest that CD97 can contribute to angiogenesis associated with inflammation and tumor progression. Strong integrin alpha5beta1 interactions with CD97 have been identified, but alpha v beta3 also contributes to cell attachment. Furthermore, soluble CD97 acts as a potent chemoattractant for migration and invasion of human umbilical vein endothelial cells (HUVECs), and this function is integrin dependent. CD97 EGF-like repeat 4 is known to bind chondroitin sulfate. It was found that coengagement of alpha5beta1 and chondroitotin sulfate proteoglycan by CD97 synergistically initiates endothelial cell invasion. Integrin alpha5beta1 is the first high-affinity cellular counterreceptor that has been identified for a member within this family of adhesion receptors.
 ...
PMID:CD97, an adhesion receptor on inflammatory cells, stimulates angiogenesis through binding integrin counterreceptors on endothelial cells. 1557 72

Lumican is a member of the small leucine-rich proteoglycan (SLRP) family and participates in the maintenance of tissue structures and tumor growth. Neuroendocrine cell tumors (NETs) including carcinoid tumors and NE cell carcinomas (NECs) possess numerous neuroendocrine (NE) granules, and differences between these tumors are in terms of their biological and metastatic aggressiveness during tumor progression. The purpose of this study was to examine the expression of lumican in NETs, and to determine whether the presence of lumican may be associated with the growth of NETs by comparing its expression between carcinoid tumors and NECs. Immunohistochemically, the positivity rates of lumican expression in the cytoplasm of the tumor cells were 87.5% in carcinoid tumors and 37.5% in NECs. Those of lumican expression in the stroma adjacent to the tumors were 90.1% in carcinoid tumors and 79.2% in NECs. In situ hybridization analysis revealed the lumican mRNA expression in the cytoplasm of carcinoid tumor and NEC cells. Ultrastructurally, the lumican protein was observed in the rough endoplasmic reticulum and NE granules of NETs and interspaces of collagen fibers. Furthermore, RT-PCR analysis revealed the presence of lumican mRNA in NEC cell lines. These results indicate that the higher expression level of cytoplasmic lumican in carcinoid tumors than in NECs may play a role in the slow growth of these tumors.
 ...
PMID:Different expression levels of lumican in human carcinoid tumor and neuroendocrine cell carcinoma. 1575 80

The interactions of transformed cells with the surrounding stromal cells are of importance for tumor progression and metastasis. The relevance of adipocyte-derived factors to breast cancer cell survival and growth is well established. However, it remains unknown which specific adipocyte-derived factors are most critical in this process. Collagen VI is abundantly expressed in adipocytes. Collagen(-/-) mice in the background of the mouse mammary tumor virus/polyoma virus middle T oncogene (MMTV-PyMT) mammary cancer model demonstrate dramatically reduced rates of early hyperplasia and primary tumor growth. Collagen VI promotes its growth-stimulatory and pro-survival effects in part by signaling through the NG2/chondroitin sulfate proteoglycan receptor expressed on the surface of malignant ductal epithelial cells to sequentially activate Akt and beta-catenin and stabilize cyclin D1. Levels of the carboxyterminal domain of collagen VIalpha3, a proteolytic product of the full-length molecule, are dramatically upregulated in murine and human breast cancer lesions. The same fragment exerts potent growth-stimulatory effects on MCF-7 cells in vitro. Therefore, adipocytes play a vital role in defining the ECM environment for normal and tumor-derived ductal epithelial cells and contribute significantly to tumor growth at early stages through secretion and processing of collagen VI.
 ...
PMID:Adipocyte-derived collagen VI affects early mammary tumor progression in vivo, demonstrating a critical interaction in the tumor/stroma microenvironment. 1584 Dec 11

Endocan, previously called endothelial cell specific molecule-1, is a soluble proteoglycan of 50 kDa, constituted of a mature polypeptide of 165 amino acids and a single dermatan sulphate chain covalently linked to the serine residue at position 137. This dermatan sulphate proteoglycan, which is expressed by the vascular endothelium, has been found freely circulating in the bloodstream of healthy subjects. Experimental evidence is accumulating that implicates endocan as a key player in the regulation of major processes such as cell adhesion, in inflammatory disorders and tumor progression. Inflammatory cytokines such as TNF-alpha, and pro-angiogenic growth factors such as VEGF, FGF-2 and HGF/SF, strongly increased the expression, synthesis or the secretion of endocan by human endothelial cells. Endocan is clearly overexpressed in human tumors, with elevated serum levels being observed in late-stage lung cancer patients, as measured by enzyme-linked immunoassay, and with its overexpression in experimental tumors being evident by immunohistochemistry. Recently, the mRNA levels of endocan have also been recognized as being one of the most significant molecular signatures of a bad prognosis in several types of cancer including lung cancer. Overexpression of this dermatan sulphate proteoglycan has also been shown to be directly involved in tumor progression as observed in mouse models of human tumor xenografts. Collectively, these results suggest that endocan could be a biomarker for both inflammatory disorders and tumor progression as well as a validated therapeutic target in cancer. On the basis of the recent successes of immunotherapeutic approaches in cancer, the preclinical data on endocan suggests that an antibody raised against the protein core of endocan could be a promising cancer therapy.
 ...
PMID:Endocan or endothelial cell specific molecule-1 (ESM-1): a potential novel endothelial cell marker and a new target for cancer therapy. 1616 66

Exclude experimental models of malignant transformation employ chemical and physical carcinogens or genetic manipulations to study tumor progression. In this work, different melanoma cell lines were established after submitting a nontumorigenic melanocyte lineage (melan-a) to sequential cycles of forced anchorage impediment. The great majority of these cells underwent anoikis when maintained in suspension. After one deadhesion cycle, phenotypic alterations were noticeable in the few surviving cells, which became more numerous and showed progressive alterations after each adhesion impediment step. No significant differences in cell surface expression of integrins were detected, but a clear electrophoretic migration shift, compatible with an altered glycosylation pattern, was observed for beta1 chain in transformed cell lines. In parallel, a progressive enrichment of tri- and tetra-antennary N-glycans was apparent, suggesting increased N-acetylglucosaminyltransferase V activity. Alterations both in proteoglycan glycosylation pattern and core protein expression were detected during the transformation process. In conclusion, this model corroborates the role of adhesion state as a promoting agent in transformation process and demonstrates that cell adhesion disturbances may act as carcinogenic stimuli, at least for a nontumorigenic immortalized melanocyte lineage. These findings have intriguing implications for in vivo carcinogenesis, suggesting that anchorage independence may precede, and contribute to, neoplastic conversion.
 ...
PMID:Melanocyte transformation associated with substrate adhesion impediment. 1661 17

The topic about the role of sulfated oligosaccharides in carcinogenesis and progression of tumor remains controversial. The present review aims to evaluate the role of sulfated oligosaccharides in carcinogenesis and progression of tumor. The modification of sulfated oligosaccharides, especially chondroitin sulfate and heparan sulfate, is an important event in carcinogenesis and is correlated with the degree of differentiation. Enhance of chondroitin sulphate may promote carcinogenesis, while enhance of heparin sulphate may promote metastasis. Resistance of antiproliferation activity of sulfated oligosaccharides may contribute to the aberrant behavior of the cancer cell. Some researches supported that sulfated proteoglycan on the cell surface may enhance metastasis; while some soluble sulfated oligosaccharides could suppress metastasis. Thus, sulfated oligosaccharides play double roles, promoter or inhibitor, in carcinogenesis and tumor progression. Four topics about the correlation between sulfated oligosaccharides and carcinogensis and progression are very interesting and must be identified: whether the modified sulfated oligosaccharides have a different effect from the unmodified sulfated oligosaccharides; whether different sulfate oligosaccharides have the different action; whether the function of sulfated proteoglycan on the cell surface is different from that of soluble sulfated oligosaccharides; whether the function of sulfated oligosaccharides in primary tumor is different from that in metastasis tumor. Further data on the long-term safety of sulfate oligosaccharides for cancer patients are therefore required to allow overall risk-benefit assessments.
 ...
PMID:Sulfated oligosaccharides and tumor: promoter or inhibitor? 1663 29

Emerging data in myeloma and other cancers indicates that heparan sulfate proteoglycans promote tumor progression by enhancing their growth and metastasis. By acting as key regulators of cell signaling via their interactions with multiple growth and angiogenic factors, heparan sulfates mediate a shift in the microenvironment that supports the tumor as an 'organ' and promotes an aggressive tumor phenotype. In addition, enzymatic remodeling of heparan sulfate proteoglycans provides a mechanism for rapid, localized and dynamic modulation of proteoglycan function thereby tightly regulating activities within the tumor microenvironment. New data from animal models demonstrates that heparan sulfate or the enzymes that regulate heparan sulfate are viable targets for cancer therapy. This strategy of targeting heparan sulfate may be particularly effective for attacking cancers like myeloma where extensive genetic chaos renders them unlikely to respond well to agents that target a single signaling pathway.
 ...
PMID:Syndecan-1: a dynamic regulator of the myeloma microenvironment. 1802 90


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