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 investigated the inhibitory effect of the N-terminal modified Arg-Gly-Asp-Ser (RGDS) analogues, AcDRGDS and AcDRLDS, on tumor cell adhesion to the components of extracellular matrix and basement membrane, and also tested the antimetastatic effect of their conjugates with trimesic acid, Ar(DRGDS)3 and Ar(DRLDS)3. AcDRGDS significantly inhibited tumor cell adhesion to fibronectin, vitronectin and RGDS substrates, but not to CS1 substrate which is a ligand for the alpha 4 beta 1 tumor surface integrin receptor. In contrast, AcDRLDS variant peptide significantly inhibited tumor cell adhesion to laminin, in addition to RGDS-mediated adhesion to fibronectin and vitronectin. AcDRLDS also inhibited tumor cell adhesion to CS1 as well as the RGDS sequence within the fibronectin molecule in a concentration-dependent manner, although the inhibitory effect was less than that of the CS1 (EILDV) peptide. Ar(DRLDS)3 inhibited the laminin- and fibronectin-mediated invasion and migration of tumor cells, whereas Ar(DRGDS)3 selectively inhibited fibronectin-mediated invasion and migration. Ar(DRGDS)3 and Ar(DRLDS)3 were much more effective in inhibiting experimental lung or liver metastases of various types of murine and human tumors than the original RGDS-containing peptides or Ar(COONa)3. Multiple administrations of Ar(DRGDS)3 or Ar(DRLDS)3 potently inhibited spontaneous lung metastasis produced by intra-footpad injection of B16-BL6 cells without affecting the primary tumor size at the time of surgical excision, as compared with RGDS peptide or untreated control. Thus, Ar(DRGDS)3 and Ar(DRLDS)3 substantially increased the exhibiting any antimetastatic effect of the peptides without direct cytotoxicity.
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PMID:Antimetastatic activities of synthetic Arg-Gly-Asp-Ser (RGDS) and Arg-Leu-Asp-Ser (RLDS) peptide analogues and their inhibitory mechanisms. 878 88

Tumor invasion of basement membranes is a complex multi-step process. Altered adhesion, as well as increased cell locomotion contribute to tumor cell invasion and metastasis. A variety of in vitro models have been used to measure cell invasiveness. The invasion of basement membranes can be simulated in vitro in blind well Boyden Chambers using the reconstituted basement membrane matrigel or collagen type I as the invasion barrier. The aim of our study was to compare the migration and invasive capacity of epidermal tumor cells (TR 131, TR 146, SCL II, FaDu, HLaC 79) and melanoma cells derived from primary tumors (Mel Ei, Mel Ho, Mel Juso, Mel Wei) or their metastases (Mel Ju, Mel Im, Sk Mel 1, Sk Mel 28). Chemotactic response of epidermal tumor cells was increased toward fibroblast conditioned medium and fibronectin (20 micrograms/ml), while laminin (100 micrograms/ml) stimulated chemotaxis in only 3 epidermal tumor cell lines (HLaC 79, FaDu, TR 146), EGF (10 ng/ml) in only 4 cases (SCL II, FaDu, TR 131, TR 146), and interleukin-1 (IL-1) in only 1 case (FaDu). Epithelial tumor cell conditioned medium had no chemotactic influence on epithelial tumor cells. Fibroblast conditioned medium, fibronectin, EGF and PDGF were potent chemoattractants for all melanoma tumor cells, whereas IL-1 did not induce a significant chemotactic response. While two epithelial tumor cell lines (FaDu, TR 146) were able to penetrate collagen type I, matrigel was an impenetrable barrier for all epithelial tumor cells. Two cell lines from melanoma primary tumors (Mel Ho, Mel Ei) and two cell lines from melanoma metastases (Sk Mel 1, Sk Mel 28) showed no invasion through collagen type I and matrigel, whereas invasion through both barriers could be observed for the metastatic cell lines Mel Ju and Mel Im and in the primary tumor cell line Mel Wei. Therefore, the clinical observation of late and rare metastasis in epithelial tumors and early metastasis in melanoma correlate with our in vitro investigation of invasive behavior in tumor cells. No significant correlation between the invasiveness of melanoma cell lines and their clinical origin could be demonstrated suggesting the existence of subpopulations with varying invasive potential.
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PMID:Comparison of migration and invasiveness of epithelial tumor and melanoma cells in vitro. 881 43

Since the adhesive interaction between tumor cells and host cells, or extracellular matrix (ECM), presumably plays a crucial role in metastatic formation during a series of complex events, we used synthetic or recombinant polypeptide analogues, poly(RGD) or CH-271-based on Arg-Gly-Asp(RGD) sequence or functional domains in fibronectin. Use of these analogues regulated the mechanisms involved in cell adhesion during the metastatic process. Poly(RGD) effectively inhibited the experimental lung and liver metastasis when coinjected i.v. with different types of tumors. In a spontaneous lung metastasis model using B-16-BL6 melanoma, multiple administrations of this polypeptide, before or after surgical excision of the primary tumor, resulted in significant inhibition of tumor metastasis without affecting the growth of the primary tumor. Further, it substantially prolonged the survival time of mice. The mechanism responsible for the inhibition of tumor metastasis by the polypeptides is partly associated with the ability to interfere with cell functions such as adhesiveness, motility, and invasiveness in the cellular adhesive process of metastasis. The combination of CH-271 fusion polypeptide and anticancer drugs, i.e., anti-adhesion therapy and chemotherapy, caused a dramatic inhibition of lung and liver metastasis of tumors when compared with either treatment alone, or in the control. Since the polypeptides derived from cell adhesion molecules showed no short-term toxicity to the host, they may provide a promising approach for the control of cancer metastasis.
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PMID:Prevention of cancer metastasis in mice with fibronectin-related substances. 898 70

A case of myofibrosarcoma of the breast is described. A 55-year-old woman presented with a small mammary nodule. A large recurrent lesions appeared a month later, and the patient died 11 months following initial presentation from diffuse pleuropulmonary metastases. Histologically, the primary tumor consisted mainly of spindled cells, arranged in fascicles and surrounded by varying quantities of dense hyaline collagen. The recurrent lesion had a more pleomorphic organization. In both lesions, there was positive immunostaining for vimentin, smooth-muscle actin, and fibronectin, and negative results for desmin, laminin, and type IV collagen. Electron microscopy revealed abundant rough endoplasmic reticulum, myofilaments with focal densities, and the fibronexus junctions and fibronectin fibrils characteristic of myofibroblasts. Given these cellular features and behavior, the tumor was interpreted as a malignant neoplasm showing myofibroblastic differentiation, i.e., a myofibrosarcoma. This case enlarges the group of myofibrosarcoma of breast, also with the demonstration of fibronexus and fibronectin fibrils. The paper emphasizes the criteria required for myofibroblastic differentiation and reviews lesions of the breast reported in the literature as myofibroblastic.
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PMID:Myofibrosarcoma of the breast: review of the literature on myofibroblastic tumors and criteria for defining myofibroblastic differentiation. 913 Sep 98

The adhesive interaction between tumor cells and host cells or the extracellular matrix plays a crucial role in metastasis formation. Therefore, understanding the mechanism controlling metastasis may assist in the development of antimetastatic therapy. We have used synthetic or recombinant polypeptide analogues containing the Arg-Gly-Asp (RGD) sequence found in the functional domains of fibronectin, such as poly(RGD) or CH-271, to regulate the mechanisms involved in cell adhesion during the metastatic process. Poly(RGD) inhibited experimental lung and liver metastasis effectively when coinjected i.v. with various types of tumors. In a model of spontaneous lung metastasis using the B16-BL6 melanoma, repeated administration of this polypeptide before or after surgical excision of the primary tumor resulted in a significant inhibition of tumor metastasis without affecting the growth of the primary tumor and substantially prolonged the survival time of mice. The mechanism responsible for the inhibition of tumor metastasis by the polypeptides is at least partly associated with the ability to interfere with cellular functions such as adhesiveness, motility and invasiveness in the process of metastasis. Combined treatment of the CH-271 fusion polypeptide and anticancer drugs, i.e., anti-adhesion therapy combined with chemotherapy, caused a marked inhibition of lung and liver metastasis of tumors as compared with either treatment alone or with the control. In contrast, the promotion of tumor cell interaction with immune cells via cell adhesion molecules, which differs from the anti-adhesive mechanism, may lead to the induction of anti-tumor immune responses and, consequently, to the inhibition of tumor metastasis. The transfection of the gene of the B7-1 adhesion molecule into tumor cells (B16-BL6 or K1735-M2 melanoma) resulted in the remarkable reduction of lung metastasis caused by the i.v. injection into mice. Immunization of B7-transfected tumor was effective as a tumor vaccine for preventing the metastasis of B7 negative original tumor cells. Thus, the regulation of the adhesive interaction with tumor cells may provide a new and promising approach for the control and prevention of cancer metastasis.
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PMID:Cell adhesion molecules and cancer metastasis. 943 54

One of the principle targets for metastasis of follicular thyroid carcinoma (FTC) is the skeleton. Because no data are available on the role of the integrin adhesion molecule family in the attachment of FTC to bone, we studied the attachment characteristics of three FTC cell lines to bone and the role of integrins. Three cell lines were used from the same patient, one (FTC-133) from the primary tumor and two (FTC-236 and FTC-238) from metastases. Attachment of FTC cell lines to bone was assessed on conditioned medium of an osteoblastic cell line, coated onto plastic, as an in vitro model of bone matrix. The synthetic RGD (Arg-Gly-Asp) peptide GRGDS impaired attachment of the FTC cell lines to bone matrix, demonstrating the role of integrins in the attachment of FTC to bone. Attachment of FTC-133 to bone matrix was blocked completely by GRGDS, whereas attachment of FTC-236 and FTC-238 could not be impaired completely. Semiquantitative polymerase chain reaction (PCR) of cDNA from the cell lines indicated stronger expression of alpha5 integrin mRNA in FTC-133 than in the other cell lines. In line with this, attachment of FTC-133 to bone matrix could be inhibited almost completely by anti alpha5 and beta1 integrin antibodies, indicating the importance of the fibronectin receptor in the attachment of FTC-133 to bone. Binding of FTC-236 and FTC-238 to bone matrix could not be inhibited completely by anti-integrin antibodies, suggesting an additional role of nonintegrin adhesion molecules in the attachment of FTC-236 and FTC-238 to bone. The synthetic bone sialoprotein cyclic peptide, CNB, revealed antiadhesive effects in the binding of FTC to bone. In conclusion, integrins play an important role in the attachment of metastatic FTC to bone. Differences in the functional involvement of integrins in the attachment to bone are observed between the three cell lines studied. From the present results, antiadhesive interventions with synthetic RGD peptides in FTC may be designed.
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PMID:Role of integrins in the attachment of metastatic follicular thyroid carcinoma cell lines to bone. 949 50

Proteases of the plasminogen-plasminogen activator (PA) system play an important role in cancer metastasis. We have examined the expression of these proteases and their cell surface receptors and inhibitors in neuroblastoma, a tumor that originates in cells of the neural crest and is the second most common solid tumor in children. This analysis was performed in seven established human cell lines and 20 primary tumor specimens. Urokinase PA and, in particular, tissue-type PA were expressed in cell lines and in tumor tissues; however, their levels of expression did not correlate with clinical stage. There was little evidence suggesting that neuroblastoma cells concentrate PA activity at their cell surface because urokinase-type PA receptor mRNA was detected in two cell lines and in 5 of 20 tumor samples by reverse transcription-PCR only. PA inhibitor (PAI)-2 was absent in all cell lines and tumor tissue samples examined. However, PAI-1, which was not expressed by the cell lines, was expressed by stromal cells and, specifically, endothelial cells in tumor tissue. By extending the analysis of PAI-1 expression in 64 primary tumor specimens, we found that high PAI-1 expression paradoxically correlated with metastatic stage and tumor recurrence. In vitro experiments indicated that the expression of PAI-1 by human microvascular endothelial cells was stimulated in the presence of SK-N-BE(2) human neuroblastoma cells and neuroblastoma culture medium. Recombinant PAI-1 also promoted SK-N-BE(2) cell detachment from vitronectin and migration from vitronectin toward fibronectin. From these data, we conclude that the up-regulation of PAI-1 expression in endothelial cells may promote rather than inhibit metastasis in neuroblastoma.
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PMID:The plasminogen-plasminogen activator (PA) system in neuroblastoma: role of PA inhibitor-1 in metastasis. 1009 67

Tumor cell adherence to and migration on the extracellular matrix is an important aspect of cancer progression. This interaction with the extracellular matrix is mediated primarily through the integrin class of cell adhesion molecules. We identified a restricted expression of alphavbeta3 in highly metastatic K1735M2 and of alphavbeta5 in poorly metastatic K1735C23 murine melanoma cells. The highly metastatic cells were ten times more motile on vitronectin and fibronectin and approximately three times more invasive through a reconstituted basement membrane than the poorly metastatic cells. This motility was inhibited by addition of anti-beta3 antibodies. Injection of the alphavbeta3-negative K1735C23 cells into syngeneic mice resulted in the generation of a metastatic variant (K1735C23PM) that neo expressed the alphavbeta3 complex, indicating that expression of alphavbeta3 is required for K1735 melanoma metastasis. Injection of highly metastatic K1735M2 cells in the presence of blocking antibody to beta3 reduced tumor size by approximately 80%. Treatment of the K1735M2 cells with a retroviral antisense beta3 construct significantly reduced their expression of alphavbeta3 and also reduced their motility on extracellular matrix ligands and their invasion through a reconstituted basement membrane. In contrast, when the K1735C23 cells were treated with a construct containing the full-length beta3 cDNA, their motility on extracellular matrix proteins and invasion of a reconstituted basement membrane were significantly increased. These results indicate that alphavbeta3 is required for migration and invasion of K1735 melanoma cells in vitro and primary tumor growth and metastasis in vivo.
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PMID:Differential expression of alphav integrins in K1735 melanoma cells. 1020 46

The generation of vascular stroma is essential for solid tumor growth and involves stimulatory and inhibiting factors as well as stromal components that regulate functions such as cellular adhesion, migration, and gene expression. In an effort to obtain a more integrated understanding of vascular stroma formation in breast carcinoma, we examined expression of the angiogenic factor vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF); the VPF/VEGF receptors flt-1 and KDR; thrombospondin-1, which has been reported to inhibit angiogenesis; and the stromal components collagen type I, total fibronectin, ED-A+ fibronectin, versican, and decorin by mRNA in situ hybridization on frozen sections of 113 blocks of breast tissue from 68 patients including 28 sections of breast tissue without malignancy, 18 with in situ carcinomas, 56 with invasive carcinomas, and 8 with metastatic carcinomas. A characteristic expression profile emerged that was remarkably similar in invasive carcinoma, carcinoma in situ, and metastatic carcinoma, with the following characteristics: strong tumor cell expression of VPF/VEGF; strong endothelial cell expression of VPF/VEGF receptors; strong expression of thrombospondin-1 by stromal cells and occasionally by tumor cells; and strong stromal cell expression of collagen type I, total fibronectin, ED-A+ fibronectin, versican, and decorin. The formation of vascular stroma preceded invasion, raising the possibility that tumor cells invade not into normal breast stroma but rather into a richly vascular stroma that they have induced. Similarly, tumor cells at sites of metastasis appear to induce the vascular stroma in which they grow. We conclude that a distinct pattern of mRNA expression characterizes the generation of vascular stroma in breast cancer and that the formation of vascular stroma may play a role not only in growth of the primary tumor but also in invasion and metastasis.
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PMID:Vascular stroma formation in carcinoma in situ, invasive carcinoma, and metastatic carcinoma of the breast. 1035 37

Fusion of Cloudman S91 melanoma cells with macrophages results in hybrids with increased metastatic potential. Here, we report that such hybrids acquire new pathways for motility. Compared to parental melanoma cells and low metastatic hybrids, the metastatic hybrids showed far stronger responses to 3T3- and lung fibroblast-conditioned media, primary lung slices, fibronectin (FN), and a Mr 120,000 FN fragment and, unlike parental cells, were further stimulated by pretreatment with melanocyte-stimulating hormone/1-methyl-3-isobutylxanthine. Hybrid migration was due primarily to chemotaxis, with chemokinesis being a minor component. Thus, the metastatic hybrids acquired melanocyte-stimulating hormone-inducible motility, perhaps reflecting the FN fragment chemotaxis of macrophages. The results support a long-standing hypothesis that metastasis is initiated following hybridization between tumor-invading phagocytes and cells of the primary tumor.
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PMID:Acquired melanocyte stimulating hormone-inducible chemotaxis following macrophage fusion with Cloudman S91 melanoma cells. 1043 19

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