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)

The injection of B16F10 melanoma cells with recombinant human tumor necrosis factor alpha (TNF-alpha) into the tail vein of C57BL/6 mice resulted in 2- to 25-fold more metastatic foci in the lungs than the injection of tumor cells alone. Clearly, TNF-alpha significantly enhanced experimental tumor metastasis. Furthermore, it enhanced the metastasis of Lewis lung carcinoma cells. In contrast, a mutein of TNF-alpha, designated as F4236, having the cell-adhesive sequence (Tyr-Ile-Gly-Ser-Arg) at the N-terminus of the TNF molecule did not enhance metastasis, but rather exhibited similar antitumor activity to wild-type TNF-alpha in fibrosarcoma-bearing mice.
Clin Exp Metastasis 1992 Jul
PMID:A YIGSR-containing novel mutein without the detrimental effect of human TNF-alpha of enhancing experimental pulmonary metastasis. 161 34

Tumor cells attach, degrade, and migrate through basement membranes as they metastasize. Laminin, a major glycoprotein of basement membranes, promotes the metastatic activity of tumor cells by stimulating the attachment and migration of the cells and their secretion of collagenase IV. We have identified a synthetic peptide of 19 amino acids (Cys-Ser-Arg-Ala-Arg-Lys-Gln-Ala-Ala-Ser-Ile-Lys-Val-Ala-Val-Ser-Ala-Asp -Arg) from the sequence of the A chain of laminin that increases experimental metastases of the lungs by murine melanoma cells. The peptide is active when injected either intravenously or intraperitoneally. The peptide increased collagenase IV activity, a key enzyme in the breakdown of basement membranes, to the same extent as laminin. This peptide represents an active site on laminin for promotion of the metastatic phenotype and generates a probe for studying the regulation of malignant activities.
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PMID:Identification of an amino acid sequence from the laminin A chain that stimulates metastasis and collagenase IV production. 215 66

Small cell lung cancer (SCLC) is a fatal malignancy due to its propensity to metastasize widely and to reoccur after chemotherapy in a drug-resistant form. While most SCLC cell lines are anchorage independent for growth, laminin induced the attachment of five of six SCLC cell lines tested (NCI-N417, NCI-H345, NCI-H146, NCI-H187, NCI-H510, and NCI-H209). NCI-N417 SCLC cells adopted a flattened morphology on laminin, and a classic SCLC cell line (NCI-H345) demonstrated a neuron-like appearance while the other SCLC cell lines except NCI-H187 cells, attached but did not spread. Adhesion to laminin was associated with increased resistance to several cytotoxic drugs. Matrigel, an extract of basement membrane proteins, greatly accelerated tumor growth when coinjected with SCLC cells in athymic mice. A synthetic peptide from the B1 chain of laminin, cyclic-YIGSR (Tyr-Ile-Gly-Ser-Arg), inhibited laminin-induced SCLC cell adhesion and migration in vitro and reduced the size of the tumors they formed when coinjected with matrigel and YIGSR. These results suggest that the interaction of SCLC cells with laminin and possibly with other basement membrane proteins can enhance their tumorigenicity and drug resistance.
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PMID:Reconstituted basement membrane (matrigel) and laminin can enhance the tumorigenicity and the drug resistance of small cell lung cancer cell lines. 216 54

Previously we reported that a pentapeptide (Tyr-Ile-Gly-Ser-Arg or YIGSR) from domain III of the B1 chain of laminin is a cell attachment site with the ability to stimulate cell adhesion and migration and to block experimental metastases. Here we report studies on the activities of synthetic peptides that cover domain III and report a second biologically active peptide PDSGR from this domain with activities similar to YIGSR. We also show that cyclic YIGSR is more potent in these assays than the linear peptide as expected since this sequence on laminin is bracketed by cysteines. Due to their proximity and similar spectrum of activities, it is possible that these sequences act in concert in the native laminin molecule.
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PMID:Identification of a second active site in laminin for promotion of cell adhesion and migration and inhibition of in vivo melanoma lung colonization. 273 66

Some malignant tumors of soft tissues that metastasize to bones are characterized by an insignificant increase in the levels of certain amino acids in the serum of the host. Primary malignant bone tumors, on the other hand, tend to increase significantly the concentration of amino acids in the host serum. We found that malignant transformation of bones, cartilage, and connective tissue induced changes in the metabolism of the patients which led to a significant elevation of several amino acids in their serum. Only alanine and cysteine showed a decreased level in the sera of patients with bone tumors. A significant increase in the concentration of amino acids in the sera of patients with bone tumors, as compared to control subjects, was found in serine, glutamine, leucine, isoleucine, lysine, arginine, and histidine (p less than 0.001). The elevated levels of serine and glutamine suggest their possible use in diagnostics, differential diagnostics, and in the study of therapeutic effects in these malignancies.
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PMID:The role of serine and glutamine in the metabolism of malignant bone tumors and their significance in the diagnosis and prognosis of bone tumors. 313 89

Our previous study revealed that mutations of the p53 gene were detected by cDNA sequencing in one of four (25%) primary gastric tumors and in five of six (83%) gastric cancer cell lines. It was of interest that all five cell lines established from metastatic lesions had p53 gene mutations, while the single cell line established from a primary tumor lacked an abnormality. Thus, the current study was initiated to determine the frequency of p53 mutations in 10 pairs of samples from primary gastric carcinomas and their lymph node metastases, in addition to morphologically normal gastric mucosa. In addition, we correlated the findings with other relevant molecular markers including the metastasis associated nm23-H1 gene and loss of heterozygosity (LOH) using multiple polymorphic markers for chromosome 17p and sequencing the entire open reading frame (ORF) of the p53 gene. Five of ten (50%) patients were constitutionally heterozygous for one or more 17p and/or p53 probes (pYNZ 22, BamHI RFLP; pMct35.1, Mspl RFLP; php53cl, Bg/II RFLP), while none had LOH at the 17p and/or p53. A Bg/II RFLP for analysis of possible nm23-H1 somatic allelic deletion revealed no LOH out of four informative cases. One paired sample demonstrated the substitution of valine for isoleucine at codon 41 (GTT to ATT) in both primary gastric tumor and metastasis. Another metastatic sample demonstrated the substitution of proline for threonine at codon 278 (CCT to C/ACT) in addition to a non-mutated codon, while only the wild-type p53 sequence was present in the paired primary gastric tumor tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of p53 gene mutations in paired primary and metastatic gastric tumor tissues. 790 5

We have used reconstituted basement membrane molecules which have formed into barriers in order to investigate the invasive potential of malignant bone and soft tissue tumour cells in vitro. A number of cell lines established from human malignant tumours demonstrated a high degree of invasiveness, although fibroblasts showed no ability to penetrate the basement membrane barrier. H-ras oncogene transfected cells into the fibroblasts were much more invasive than the parent lines. Primary cultures of malignant tumour cells demonstrated invasiveness, while those of nonmetastatic cells and fibroblasts did not. The binding of tumour cells to laminin in the basement membranes was found to induce secretion of collagenase and motility which are crucial factors for invasion. A synthetic peptide, Tyr-Ile-Gly-Ser-Arg, was able to suppress the invasiveness of HT1080 human fibrosarcoma cells, and also reduced lung colonisation in vitro. The results suggest that the in vitro assay was useful, firstly to determine the invasive potential, secondly to investigate the mechanism of invasion, and finally to development treatment against invasion and metastases.
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PMID:In vitro assay of the invasive potential of malignant bone and soft tissue tumours through basement membranes. 800 14

Basement membrane has a variety of effects on tumor cells and promotes malignant behavior. Tumor cell growth is enhanced both in vitro and in vivo in mice in the presence of basement membrane. This has led to the ability to grow various tumors including human biopsy specimens in nude mice. Furthermore, low cell numbers can be used when coinjected with Matrigel, a basement membrane extract. The basement membrane glycoprotein laminin is important in promoting invasive behavior and the level of a 32/67 kDa laminin receptor has been shown to correlate with malignancy. A sequence of five amino acids, tyrosine-isoleucine-glycine-serine-arginine (YIGSR) has been shown to recognize this receptor and to reduce experimental metastases (tail vein injection resulting in colonization of the lung) and subcutaneous tumor growth. This peptide is active in both models either when coinjected or when daily intraperitoneal injections are given after tumor growth has initiated. YIGSR does not effect cell arrest but does inhibit angiogenesis which is necessary for tumor growth. YIGSR also appears to have an additional antitumor effect via its interaction with a specific receptor. YIGSR-adherent cells established after 30 successive selections on YIGSR-coated dishes in vitro formed more lung colonies after intravenous injection and larger tumors after subcutaneous injection than the parent B16F10 melanoma cells. The YIGSR-non-adherent cells formed fewer lung colonies and smaller subcutaneous tumors. These data demonstrate the importance of laminin-tumor cell interactions in malignancies and suggest that a short sequence from laminin has multiple effects in reducing tumor growth and spread.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of Matrigel and laminin peptide YIGSR on tumor growth and metastasis. 840 Jan 43

This study was conducted to determine the mechanisms for the enhanced inhibitory effect of cell-adhesive peptides conjugated to polyethylene glycol (PEG) on tumor metastasis. Tyr-Ile-Gly-Ser-Arg (YIGSR), a laminin-derived peptide, conjugated with amino-PEG (YIGSR-aPEG) inhibited lung metastasis of B16-BL6 melanoma cells more effectively than unconjugated YIGSR peptide. [125I]-YIGSR-aPEG and native [125I]-YIGSR showed similar biphasic elimination and profiles after intravenous injection into C57BL/6 mice. Both [125I]-YIGSR and [125I]-YIGSR-aPEG expressed similar plasma half-lives and organ distributions. The radioactivity of both compounds was transported rapidly from the blood to the kidneys, and immediately excreted into the urine. [125I]-YIGSR was almost completely degraded in the urine, but [125I]-YIGSR-aPEG was not. In an in vitro stability assay, [125I]-YIGSR was degraded immediately upon incubation with mouse serum, whereas [125I]-YIGSR-aPEG was not degraded after 180 min incubation in mouse serum. These findings indicate that the enhanced inhibitory effect of YIGSR-aPEG on lung metastasis might be due to its increased stability in the blood.
Invasion Metastasis 1995
PMID:Synthetic cell-adhesive laminin peptide YIGSR conjugated with polyethylene glycol has improved antimetastatic activity due to a longer half-life in blood. 862 Dec 71

This paper describes the synthesis and biological evaluation of six partial retro-inverso peptidomimetic analogs of YIGSR-NH2, a synthetic peptide from the beta 1 chain of laminin, which has antimetastatic activity. The intent was to improve the antimetastatic potency of YIGSR-NH2 by limiting the in vivo enzymatic degradation through the incorporation of fraudulent peptide bonds. We have prepared the following retro-inverso peptides, Tyr-Ile-Gly-Ser-gArg-CHO (1), Tyr-gIle-mGly-Ser-Arg-NH2 (2), Tyr-gIle-mGly-Ser-gArg-CHO (3), gTyr-D-rIle-mGly-Ser-Arg-NH2 (4), Tyr-Ile-Gly-gSer-D-rArg-CHO (5) and Tyr-gIle-rGly-D-rSer-D-rArg-CHO (6). In vitro assays for B16F10 melanoma cell adhesion showed no significant activity for these six peptides. Peptides 1-3, 5 and 6 were further tested, in vivo, for their ability to inhibit tumor metastases to the lung in mice injected in the tail vein with B16F10 melanoma cells. All five of the retro-inverso peptides tested showed statistically significant inhibition of metastasis, but the most active peptides were 5 and 6, which showed 57 and 69% inhibition of metastasis, respectively.
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PMID:Synthesis and activity of partial retro-inverso analogs of the antimetastatic laminin-derived peptide, YIGSR-NH2. 915 Dec 57


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