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)

Frozen tissue sections obtained from human glioblastomas, brain tumor metastases and normal brain were examined for the expression of molecules known to be involved in lymphocyte activation and/or adhesion and migration. The molecules studied included CD3, CD45R, UCHL-1 (CD45RO), lymphocyte function-associated antigen 1 (LFA-1) (CD11a, CD18), intercellular adhesion molecule 1 (ICAM-1) (CD54), 4B4 (CD29), CD44, CD2, and LFA-3 (CD58). CD3+ lymphocytes infiltrating human glioblastomas and brain tumor metastases expressed LFA-1 alpha and beta. Many cells were also UCHL-1+ whereas only a small percentage were CD45R+. CD2+ lymphocytes were also present. Tumor-infiltrating lymphocytes (TIL) were found to be negative for CD29, which was, however, expressed on intratumoral vessels in addition to vessels found in normal brain. Glioblastoma cells and intratumoral vessels expressed ICAM-1 whereas no ICAM-1 was found on TIL or on normal brain. Glioblastoma cells also expressed high levels of both CD44 and LFA-3 whereas TIL were negative for these antigens. CD44 was also expressed on certain regions of normal brain. Antibodies to LFA-1 alpha and -beta and ICAM-1 could significantly block the binding of lymphokine-activated killer (LAK) cells or TIL to human glioblastoma cells suggesting that these molecules play a role in the binding and subsequent migration of lymphocytes into brain tumor tissue.
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PMID:Activation and adhesion molecule expression on lymphoid infiltrates in human glioblastomas. 169 16

Current evidence indicates that the localization and extravasation of neutrophils is a complex process involving several adhesion molecules with apparently distinct functions, and a highly coordinated and dynamic interplay between the neutrophil and the endothelial cell that is influenced by the shear forces present at the interface between these two cell types. Chemotactic stimulation of the neutrophil not only induces directed locomotion but markedly alters the surface expression and functions of the neutrophil adhesion molecules, having both an upregulating and downregulating influence. Cytokines such as interleukin 1 induce the synthesis and surface expression of endothelial adhesion molecules such as ICAM-1 and ELAM-1, and stimuli such as thrombin and histamine induce the rapid mobilization to the endothelial surface of another adhesion molecule, GMP-140. Transendothelial migration of neutrophils in most settings both in vitro and in vivo appears to require CD18 integrins on the neutrophil and ICAM-1 on the endothelial cells. This is most clearly demonstrated by the genetic deficiency of CD18 in humans, dogs and cattle, where neutrophil extravasation at most inflammatory sites is almost completely absent. Though the coordinated functions of the various neutrophil and endothelial adhesion molecules are highly efficient in promoting neutrophil extravasation, there has been relatively little investigation of their utilization in tumor cell dissemination. Recent results indicate that such studies may prove fruitful. For example, some adenocarcinoma cell lines express the complex carbohydrate (sialyl Lewis x) recently shown to be a ligand for ELAM-1.
Cancer Metastasis Rev 1991 May
PMID:PMN adhesion and extravasation as a paradigm for tumor cell dissemination. 191 73

We evaluated the expression of the cell-adhesion molecules (CAM) that might be involved in liver-associated lymphocyte (LAL) contacts with other sinusoidal cells and/or be responsible for natural-killer(NK)- and lymphokine-activated killer(LAK) activity in patients with liver metastasis. The LAL population was isolated by sinusoidal high-pressure lavage from partial hepatectomies obtained from patients operated for metastases (n = 13) and benign liver tumors (n = 9). Surface expression of the beta-2-integrin chains (CD11a, CD11b, CD11c and CD18), and the beta-I-integrin chains (CD49b, CD49d, CD49f and CD29), as well as that of members of the immunoglobulin superfamily (CD2, CD54, CD56 and CD58), were analyzed by one- or two-color flow cytometry. Quantitative and qualitative differences were observed in both groups of patients in the expression of CAM between LAL and peripheral blood lymphocytes (PBL). LAL were characterized by an increase in the percentage of CD11b-, CD49b-, CD49d-, CD54-, CD56- and CD58-positive cells in comparison with PBL. Fluorescence values for CD2, CD11a, CD18 and CD56 were higher in LAL than in PBL. Moreover, the population expressing these antigens of differentiation presented a bimodal distribution (dim and bright): in LAL, as opposed to PBL, the percentage of cells with a bright phenotype was greater than of those with a dim one. The increase in CAM expression on LAL could be due to the influence of the liver sinusoidal micro-environment. Results were more unexpected for the comparison between benign and malignant tumors. No difference was found in CAM expression on LAL between these 2 categories. Consequently, it cannot be this factor that explains the decrease in LAK activity of LAL in patients with metastasis.
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PMID:Variations in the expression of cell-adhesion molecules on liver-associated lymphocytes and peripheral-blood lymphocytes in patients with and without liver metastasis. 775 52

Treating human malignant melanoma cells with tumor necrosis factor-alpha (TNF-alpha) or interferon-gamma (IFN-gamma) causes a dose- and time-dependent increase in surface expression of ICAM-1. Increased ICAM-1 expression corresponds to greater binding of human leukocyte functional antigen-1 (CD11a/CD18)-expressing peripheral blood mononuclear cells (PBMC) to C8161 monolayers, suggesting that cytokine-treated melanoma cells would be more metastatic due to PBMC-tumor cell emboli. The purpose of this study was: (1) to test whether TNF-alpha-treated human melanoma cells are indeed more metastatic than untreated C8161 and (2) to determine whether ICAM-1 plays a role in metastasis of C8161. When surface ICAM-1 expression is upregulated, formation of lung metastases in nude mice increases 1.5- to 4-fold (P < 0.05) for human melanoma cell lines C8161, MeWo, and A375. Treatment of C8161 with ICAM-1 phosphorothioate antisense oligonucleotides using cationic lipids results in > 90% inhibition of ICAM-1 surface expression as determined by ELISA and flow cytometry. Antisense ICAM-1-treated cells form 41-64% fewer metastases than sham-treated cells. Metastasis does not increase when antisense-treated melanoma cells are exposed to TNF-alpha. However, treatment of C8161 with antisense 5-lipoxygenase (5-LO) oligonucleotides inhibits metastases 39% in Lipofectin-treated cells, but does not inhibit TNF-alpha-induced upregulation of experimental metastases. Similar experiments were performed to measure PBMC adhesion to antisense oligonucleotide-treated C8161 cells; however, TNF-alpha-inducible increase in adhesion was unaffected by ICAM-1 or 5-LO antisense oligonucleotides. These results demonstrate that ICAM-1 is involved in melanoma metastasis, but probably not at the step of PBMC adhesion to C8161 cells.
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PMID:Enhanced metastatic ability of TNF-alpha-treated malignant melanoma cells is reduced by intercellular adhesion molecule-1 (ICAM-1, CD54) antisense oligonucleotides. 791 92

In order to evaluate the significance of adhesion molecules expressed on melanocytic tumours for progression and prognosis in vivo, we studied integrin expression (VLA-1 to VLA-6, CD18, CD51, CD61) on 10 naevi, 40 primary malignant melanomas, and 11 metastases by immunohistology using the APAAP technique. Evaluation was done by grouping the percentage of positive tumour cells in six categories. Statistical analysis (Wilcoxon rank test, Scheffe test) revealed significant differences in the expression of VLA-1 (P < 0.0001), VLA-2 (P = 0.0001), VLA-5 (P = 0.0093), VLA-6 (P = 0.0232), and CD61 (P = 0.0002) between naevi and primary melanomas. Comparing primary melanomas with metastases, a statistically significant decrease in the expression of VLA-1, VLA-2, and VLA-6 was detectable, as well as a significant increase in VLA-4 and VLA-5. There was no correlation between integrin expression and tumour type (superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma), regression and ulceration. Changes of VLA-1, VLA-4, and VLA-6 expression correlated with the tumour thickness of the primary melanoma, but only VLA-4 and VLA-6 expression on primary melanomas correlated significantly with the development of metastases (P = 0.024 and P = 0.001). These changes of integrin expression during tumour progression particularly, the data showing an increase of VLA-4, and a decrease of VLA-6 expression support the concept that integrins are a new additional set of prognostic markers which indicate predisposition to the development of metastases.
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PMID:Tumour progression and metastatic behaviour in vivo correlates with integrin expression on melanocytic tumours. 810 45

To form distant metastases, tumour cells must stabilize adhesive interactions that prevent detachment at secondary sites. Primary receptor-ligand interactions alone may not maintain prolonged adhesive contacts without secondary events that lead to adhesion stabilization. Computerized imaging methods enable us to examine various substrates for: (i) the wall shear adhesion threshold (WSAT), a measure of the dynamic adhesive potential of tumour cells; (ii) the number of tumour cells that adhered; and (iii) the adhesion stabilization lag time (ASLT) or length of time required for tumour cells to stabilize adhesive contacts capable of withstanding high wall shear force (up to 100 dynes/cm2). The relative WSAT ratios found were: wheat germ agglutinin (WGA) > laminin > fibronectin > vitronectin > collagen I > collagen IV > von Willebrand factor (vWF) (the greater the shear rate the higher the adhesive potential). The relative stabilization ratios found were as follows: laminin < fibronectin < vitronectin < collagen IV < collagen I < vWF < WGA (shorter times correlate with greater stabilization potential). Stabilization data using fibronectin as a substrate correlated the best with metastatic potential. Using three melanoma lines of different metastatic potential semiquantitative reverse transcriptase-polymerase chain reaction (PCR) showed a two- to four-fold increase in alpha1, alpha3, alpha4, alpha5, alpha6, and ICAM-1 in the highly metastatic 70W cells compared to the MeWo and non-metastatic 3S5 melanoma cells. There were no differences in alphav, beta1 and beta3 levels among the three melanoma lines, and PCR products for alphaIIb, alpha2, CD36, or ICAM-2 were not detected. The 70W cells also had higher levels of alphax and beta2 (CD11/CD18 and p150 leukocyte antigen) than either the MeWo or 3S5 cells. The data indicate that melanoma cells exhibit differences in the adhesion properties under fluid shear and differences in the expression of adhesion components that correlate with their metastatic potential.
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PMID:Human melanoma integrins contribute to arrest and stabilization potential while flowing over extracellular matrix. 871 81

Eighteen metastatic nodes derived from the wild-type (GR9) and from 4 different clones (G2, D8, B10, and B9) obtained from a fibrosarcoma were analyzed for H-2 class I and II expression, as well as for adhesion molecules (CD44, CDIIb, CD18, CD49, and CD54). When metastatic nodes were cultured, typed for H-2 antigens, and compared with the H-2 expression of the inducing tumor cell, H-2 Kd and Dd class I expression was greater in most nodes analyzed. In contrast, the Ld molecule remained negative, or showed a minor increase. Class II expression was negative in the wild-type and the tumor clones, and remained so in the metastatic colonies. Analysis of the adhesion molecules revealed no differences between the inducing tumor cells and the metastatic nodes. The only molecule expressed was CD44, which was present in all cells studied and was also inducible by interferon-gamma. The increase in H-2K and H-2D expression was associated with resistance to natural killer cytotoxicity, as observed in the G2 tumor clone and some autologous metastases, such as B9MP2, G2MK2, and G2MLI. In three independent clones of this tumor system (D8, BIOMP6, and B9MP6) we found that tumor cells treated with interferon-gamma had the same altered phenotype, i.e., a selective lack of response of the Ld molecule to induction. These findings add a cautionary note to the well-established idea that tumor cells may lose all class I antigens during tumor progression, and suggest that sometimes this may not be the case. The selective downregulation of Ld and upregulation of Kd and Dd class I expression may give some tumor cells means of escaping both cytotoxic lymphocyte and natural killer immune surveillance.
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PMID:Selective upregulation of MHC class I expression in metastatic colonies derived from tumor clones of a murine fibrosarcoma. 1078 79

Systemic effects on T-cell-mediated antitumor immunity, on expression of T-cell adhesion/homing receptors, and on the promotion of T-cell infiltration of neoplastic tissue may represent key steps for the efficacy of immunological therapies of cancer. In this study, we investigated whether these processes can be promoted by s.c. administration of low-dose (0.5 microg/kg) recombinant human interleukin-12 (rHuIL-12) to metastatic melanoma patients. A striking burst of HLA-restricted CTL precursors (CTLp) directed to autologous tumor was documented in peripheral blood by a high-efficiency limiting dilution analysis technique within a few days after rHuIL-12 injection. A similar burst in peripheral CTLp frequency was observed even when looking at response to a single tumor-derived peptide, as documented by an increase in Melan-A/Mart-1(27-35)-specific CTLp in two HLA-A*0201+ patients by limiting dilution analysis and by staining peripheral blood lymphocytes (PBLs) with HLA-A*0201-melanoma antigen-A/melanoma antigen recognized by T cells (Melan-A/Mart)-1 tetrameric complexes. The CTLp burst was associated, in PBLs, with enhanced expression of T-cell adhesion/homing receptors CD11a/CD18, CD49d, CD44, and with increased proportion of cutaneous lymphocyte antigen (CLA)-positive T cells. This was matched by a marked increase, in serum, of soluble forms of the endothelial cell adhesion molecules E-selectin, vascular cell adhesion molecules (VCAM)-1 and intercellular adhesion molecules (ICAM)-1. Infiltration of neoplastic tissue by CDS+ T cells with a memory and cytolytic phenotype was found by immunohistochemistry in eight of eight posttreatment metastatic lesions but not in five of five pretreatment metastatic lesions from three patients. Increased tumor necrosis and/or fibrosis were also found in several posttherapy lesions of two of three patients in comparison with pretherapy metastases. These results provide the first evidence that rHuIL-12 can boost the frequency of circulating antitumor CTLp in tumor patients, enhances expression of ligand receptor pairs contributing to the lymphocyte function-associated antigen-1/ICAM-1, very late antigen-4/VCAM-1, and CLA/E-selectin adhesion pathways, and promotes infiltration of neoplastic lesions by CD8+ memory T cells in a clinical setting.
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PMID:Peripheral burst of tumor-specific cytotoxic T lymphocytes and infiltration of metastatic lesions by memory CD8+ T cells in melanoma patients receiving interleukin 12. 1091 69

CD43 is an integral cell membrane mucin appearing on hematopoietic cells in embryonic life probably on cells of vitellus bag, in embryonic and foetal liver and in foetal bone marrow. In adults CD43 occurs both on bone marrow hematopoietic stem cells as well as on peripheral mature white blood leukocytes with the exception of resting B lymphocytes. CD43 is also found on tissue macrophage, dendritic cells, smooth muscle cells, epithelium and endothelium. CD43 expression was detected on cells of leukaemias myeloid and lymphoid, lymphoma cells and metastases of solid neoplasms. Due to the elongated, twig-resembling shapes and numerous negatively charged rests of sialic acid CD43 can act in an anti-adhesive fashion e.g., disturbing ICAM-1 (CD54)--LFA-1 (CD11A/CD18) interaction. Alternatively, in certain conditions CD43 can be pro-adhesive. So, e.g., adhesion hematopoietic progenitor cells to stromal bone marrow cells partly depends on CD34-CD43 cooperation. Similarly, according to the degree of cell maturity and the kind of cell line, CD43 can induce either activation or cell apoptosis. So, bindig CD43 by specific monoclonal antibody induces activation and proliferation of T cells and also the oxidation burst of monocytes and neutrophils. On the other hand, CD43 induces apoptosis, especially in dividing progenitor hematopoietic stem cells.
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PMID:[Universal CD43 molecule]. 1114 90

Although synovial cell sarcoma is reported to be the most common neoplasm of the canine synovium, this retrospective study of 35 canine synovial tumors found that the majority were of histiocytic origin. Five (14.3%) synovial cell sarcomas were identified by positive immunohistochemical staining with antibodies to cytokeratin. Eighteen (51.4%) histiocytic sarcomas were identified by cell morphology and immunohistochemical staining with antibodies to CD18. Six (17.1%) synovial myxomas were identified by histologic pattern. The remaining six (17.1%) synovial tumors represented a variety of sarcomas, including two malignant fibrous histiocytomas (actin positive), one fibrosarcoma, one chondrosarcoma, and two undifferentiated sarcomas. Rottweilers were overrepresented in the histiocytic sarcoma category and Doberman Pinschers were overrepresented in the synovial myxoma category. The average survival time was 31.8 months for dogs with synovial cell sarcoma, 5.3 months for dogs with histiocytic sarcoma, 30.7 months for dogs with synovial myxoma, and 3.5 months for dogs with other sarcomas. Among the dogs with follow-up information available, metastatic disease was detected in 25% of dogs with synovial cell sarcoma, in 91% of dogs with histiocytic sarcoma, in none of the dogs with synovial myxoma, and in 100% of dogs with other sarcomas. Immunohistochemical staining for cytokeratin, CD18, and smooth muscle actin is recommended to make the diagnosis and thereby predict the behavior of synovial tumors in dogs.
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PMID:The diagnosis and prognosis of synovial tumors in dogs: 35 cases. 1201 12


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