UMLS:C0677930 - FACTA Search

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Query: UMLS:C0677930 (primary tumor)
20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have determined the prevalence of pepsinogen II (PG II) immunoreactive cells in a large series of early and advanced gastric cancers and relationships among PG II-positivity, tumor histologic type, extent of gastric wall invasion, and presence of lymph node metastases. Of the 316 cancers evaluated, 150 (47%) expressed PG II. The prevalence by histologic type was 55% in 146 glandular tumors, 43% in 83 diffuse tumors, 16% in 25 mucoid tumors, and 51% in 59 mixed-type cancers. Two parietal cell cancers and one undifferentiated cancer were PG II-negative. In glandular and diffuse cancers, but not mucoid and mixed tumors, both the extent of gastric wall invasion and incidence of lymph node metastases were associated positively with PG II expression by the primary tumor. In particular, PG II-reactive cells were found significantly more often in advanced than in early diffuse cancers (P less than 0.05) and significantly more often in submucosal early cancers than in intramucosal early cancers (P less than 0.01). The prevalence of PG II expression also was higher significantly in metastatic cancers than in nonmetastatic cancers. This was true for advanced gastric cancers as a whole (P less than 0.01), advanced glandular-type cancer alone (P less than 0.01), advanced glandular- and diffuse- type cancers together (P less than 0.001), and early diffuse-type cancer (P less than 0.05). Only four (3%) of 145 cancers evaluated for pepsinogen I (PG I) were positive, and each also was positive for PG II. The results suggest that the expression of PG II by glandular and diffuse types of gastric cancer may be a marker of increased malignancy.
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PMID:Expression of pepsinogen II in gastric cancer. Its relationship to local invasion and lymph node metastases. 333 59

The antithrombotic compound nafazatrom was evaluated in several in vivo and in vitro assays to elucidate the mechanism of its antimetastatic activity. C57BL/6 mice bearing B16 amelanotic subcutaneous tumors treated with 100 mg nafazatrom/kg/day exhibited a sixfold reduction in metastatic pulmonary lesions compared to lesion numbers in controls. The reduction in metastatic lesions was not accompanied by changes in primary tumor growth, and up to 1 microgram nafazatrom/ml did not inhibit tumor cell proliferation in vitro. Treatment of C57BL/6 mice with nafazatrom prior to iv inoculation of tumor cells failed to inhibit lung colony formation. In vitro exposure of exponentially growing B16 amelanotic cells to nafazatrom (1 microgram/ml for 72 hr) in culture did not change their ability to adhere to endothelial cell monolayers. B16 amelanotic cells degraded the matrix material of bovine endothelial cell monolayers; a heparin sulfate proteoglycan appeared to be the predominant matrix component released by these tumor cells, as judged by resistance to chondroitin ABC lyase and sensitivity to heparitinase and pronase degradation. Nafazatrom (1 microgram/ml for 72 hr) inhibited the solubilization of matrix components by approximately 60%. Tumor cell degradation of matrix components is an important event in the pathogenesis of metastasis. Thus the interference with this process appears to provide an explanation for the inhibition of malignant cell dissemination in vivo by nafazatrom.
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PMID:Interference with tumor cell-induced degradation of endothelial matrix on the antimetastatic action of nafazatrom. 345 6

The process of metastasis involves a series of sequential steps in which malignant cells are released from the primary tumor and metastasize to distant sites. Syndecan-1 is a cell surface proteoglycan that mediates cell adhesion and undergoes changes upon cell transformation of some cells that may contribute to the process of metastasis. To investigate the possible role of syndecan-1 in cell proliferation and metastatic potential, we employed a highly metastatic cell line (KLN 205) derived from mouse lung squamous cell carcinoma that expressed moderate amounts of syndecan-1. At first, endogenous syndecan-1 production was inhibited by an antisense oligodeoxynucleotides (ODNs). Since antisense ODNs of syndecan-1 inhibited cell growth, we established stable transfectants of syndecan-1 in this cell line to examine a proliferative advantage with the level of syndecan-1 expression. Overexpresser cells grew at a significantly faster rate than the vector-transfected control and showed greater incidence of tumor formation when injected subcutaneously into nude mice. Surprisingly, overexpresser cells enhanced pulmonary metastasis when injected intravenously. These results indicate that syndecan-1 expression plays a role in the control of cell proliferation and suggest that syndecan-1 expression may be involved in facilitating distant metastasis of tumor cells once they managed to enter the bloodstream (after intravasation steps).
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PMID:Altered proliferative and metastatic potential associated with increased expression of syndecan-1. 981 73

The laminin alpha5 chain is a component of laminin-10 (alpha5beta1gamma1) and -11 (alpha5beta2gamma1). In this study, we have screened 113 overlapping synthetic peptides from the laminin alpha5 globular domain (G-domain) for cell attachment activity with B16-F10 cells using peptide-coated dishes. Eleven attachment-active peptides were identified. In vivo experimental B16-F10 pulmonary metastasis and primary tumor growth assays found that 4 of the 11 peptides inhibited tumor metastasis and growth and increased apoptosis. These four peptides also blocked tumor cell migration, invasion, and angiogenesis. Two of the peptides were highly homologous and showed significant similarity to sequences in collagens. We sought to identify the B16-F10 cell surface receptors for each of the four active peptides using peptide affinity chromatography. Only one peptide recognized a cell surface protein. Peptide A5G27 (RLVSYNGIIFFLK, residues 2892-2904) bound a diffuse M(r) approximately 120,000-180,000 band that eluted with 2 m NaCl. Glycosidase digestion of the 2 m eluate yielded protein bands of M(r) 90,000 and 60,000 that reacted in Western blot analysis with antibodies to CD44. Immunoprecipitation of the A5G27-bound membrane proteins with various cell surface proteoglycan antibodies confirmed CD44 as the surface receptor for A5G27. Finally, attachment assays to A5G27 in the presence of soluble glycosaminoglycans (GAGs) identified the GAGs of CD44 as the binding sites for A5G27. Our results suggest that A5G27 binds to the CD44 receptor of B16-F10 melanoma cells via the GAGs on CD44 and, thus, inhibits tumor cell migration, invasion, and angiogenesis in a dominant-negative manner.
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PMID:Identification of an active site on the laminin alpha5 chain globular domain that binds to CD44 and inhibits malignancy. 1525 50

Expression of CA IX is normally restricted to the mucosa of alimentary tract, but on the other hand, it takes place in a high percentage of human cancers derived from tissues which are normally CA IX-negative. It is a transmembrane protein with two extracellular domains: carbonic anhydrase (CA) with a high catalytic activity and a proteoglycan-like segment (PG), mediating cell-cell adhesion. Both CA and PG domains interact with the microenvironment and they could play a role in tumorigenesis, but their roles are poorly understood. The present work characterizes some newly recognized properties of the PG. One of them is a prevalently negative charge, caused by a high proportion of dicarboxylic amino acids. This is reflected by easy dissociation of complexes formed by PG either with monoclonal antibody M75 or with the cell surface receptor already at slightly acidic pH. This property might facilitate separation of cells from the primary tumor. Released cells may subsequently attach elsewhere in the organism and eventually start metastatic growth. Another aim of the present study was to identify human tumor cell lines which are expressing the presumed CA IX receptor molecule. The same cell lines were also tested for the presence of CA IX protein; we found that expression of CA IX and of the receptor is independent of each other. In addition, we examined the species specificity of CA IX receptors. The PG domain, which contains the epitope of mAb M75 -PGEEDLP- overlapping with the binding site for putative receptor is relatively conserved in evolution: human and rat CA IX cross-react with M75 antibody on western blots. Consistently with this, human and rat cells can attach to purified human CA IX protein. On the other hand, murine CA IX contains an entirely different equivalent of PG sequence and it does not react with M75 antibody or attach to human CA IX protein. This is suggestive of the co-evolution of CA IX protein together with its receptor.
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PMID:Carbonic anhydrase IX (CA IX) mediates tumor cell interactions with microenvironment. 1580 67

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.
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PMID:Adipocyte-derived collagen VI affects early mammary tumor progression in vivo, demonstrating a critical interaction in the tumor/stroma microenvironment. 1584 Dec 11

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.
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PMID:Sulfated oligosaccharides and tumor: promoter or inhibitor? 1663 29

Decorin, a member of the small leucine-rich proteoglycan gene family, down-regulates members of the ErbB receptor tyrosine kinase family and attenuates their signaling, leading to growth inhibition. We investigated the effects of decorin on the growth of ErbB2-overexpressing mammary carcinoma cells in comparison with AG879, an established ErbB2 kinase inhibitor. Cell proliferation and anchorage-independent growth assays showed that decorin was a potent inhibitor of breast cancer cell growth and a pro-apoptotic agent. When decorin and AG879 were used in combination, the inhibitory effect was synergistic in proliferation assays but only additive in both colony formation and apoptosis assays. Active recombinant human decorin protein core, AG879, or a combination of both was administered systemically to mice bearing orthotopic mammary carcinoma xenografts. Primary tumor growth and metabolism were reduced by approximately 50% by both decorin and AG879. However, no synergism was observed in vivo. Decorin specifically targeted the tumor cells and caused a significant reduction of ErbB2 levels in the tumor xenografts. Most importantly, systemic delivery of decorin prevented metastatic spreading to the lungs, as detected by novel species-specific DNA detection and quantitative assays. In contrast, AG879 failed to have any effect. Our data support a role for decorin as a powerful and effective therapeutic agent against breast cancer due to its inhibition of both primary tumor growth and metastatic spreading.
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PMID:An antimetastatic role for decorin in breast cancer. 1868 28

Decorin, the prototype member of the small leucine-rich proteoglycans, resides in the tumor microenvironment and affects the biology of various types of cancer by downregulating the activity of several receptors involved in cell growth and survival. Decorin binds to and modulates the signaling of the epidermal growth factor receptor and other members of the ErbB family of receptor tyrosine kinases. It exerts its antitumor activity by a dual mechanism: via inhibition of these key receptors through their physical downregulation coupled with attenuation of their signaling, and by binding to and sequestering TGFbeta. Decorin also modulates the insulin-like growth factor receptor and the low-density lipoprotein receptor-related protein 1, which indirectly affects the TGFbeta receptor pathway. When expressed in tumor xenograft-bearing mice or injected systemically, decorin inhibits both primary tumor growth and metastatic spreading. In this review, we summarize the latest reports on decorin and related molecules that are relevant to cancer and bring forward the idea of decorin as an anticancer therapeutic and possible prognostic marker for patients affected by various types of tumors. We also discuss the role of lumican and LRIG1, a novel cell growth inhibitor homologous to decorin.
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PMID:Tumor microenvironment: Modulation by decorin and related molecules harboring leucine-rich tandem motifs. 1879 67

Decorin, a member of the small leucine-rich proteoglycan gene family, impedes tumor cell growth by down-regulating the epidermal growth factor receptor. Decorin has a complex binding repertoire, thus, we predicted that decorin would modulate the bioactivity of other tyrosine kinase receptors. We discovered that decorin binds directly and with high affinity (K(d) = approximately 1.5 nM) to Met, the receptor for hepatocyte growth factor (HGF). Binding of decorin to Met is efficiently displaced by HGF and less efficiently by internalin B, a bacterial Met ligand. Interaction of decorin with Met induces transient receptor activation, recruitment of the E3 ubiquitin ligase c-Cbl, and rapid intracellular degradation of Met (half-life = approximately 6 min). Decorin suppresses intracellular levels of beta-catenin, a known downstream Met effector, and inhibits Met-mediated cell migration and growth. Thus, by antagonistically targeting multiple tyrosine kinase receptors, decorin contributes to reduction in primary tumor growth and metastastic spreading.
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PMID:Decorin is a novel antagonistic ligand of the Met receptor. 1943 54

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