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 c-MET proto-oncogene encodes the receptor for the Hepatocyte Growth Factor/Scatter Factor, which is known to mediate mitogenic, motogenic and invasive responses of several cell types. We have analysed by immunohistochemistry and biochemically the expression of c-MET in benign and malignant melanocytic lesions. The Met/HGF receptor which in the melanocytic lineage displays the structural features of the authentic receptor was undetectable in tissue melanocytes and in nevocytic nevi. Only four out of 23 primary melanomas scored positive. Expression was increased to a significant level in 17 out of the 44 metastatic lesions examined. The c-MET expression was homogeneous in multiple metastases from the same patients. Comparative analyses showed both lack of correlation with the expression of the tumour progression associated ICAM-1 adhesion molecule and, in 23% of cases, co-expression with the c-KIT encoded receptor. These findings show that the c-MET gene is expressed at late stages of melanoma progression and suggest that the presence of Met/HGF receptor may contribute to the acquisition of an invasive phenotype.
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PMID:Expression of the c-Met/HGF receptor in human melanocytic neoplasms: demonstration of the relationship to malignant melanoma tumour progression. 810 62

In order to investigate the effects of in vivo treatment with interferon-alpha (IFN-alpha) on melanoma antigens, a clinical EORTC trial (No. 18852) was accompanied by an immunohistological study. Twenty patients with melanoma metastases of skin and soft tissues, eventually also of the lung, who were treated with systemic IFN-alpha, were evaluated for a comparison of metastases before (40) and during (42) treatment. Representative cryostat sections were studied immunohistologically with a panel of monoclonal antibodies against differentiation antigens (HMW-MAA, K-1-2, NKI-beteb, M-2-10-15), progression markers (transferrin receptor, ICAM-1, VLA-2), histocompatibility antigens (HLA-A, B, C, HLA-DR) and the proliferation-associated nuclear antigen Ki67. We found an overall reduction of the proliferation-associated antigen Ki-67 (p < 0.01), and an increase in expression of HLA-DR (p < 0.05) and ICAM-1 (trend) during treatment. The intensity of expression of HLA-A, B and C antigens as well as pigmentation (p < 0.01) was found to be increased. Early progression (< or = 8 weeks after onset of treatment) was associated with a lack of phenotypic changes. The data suggest an independent modulation of proliferation, pigmentation, and antigen expression by systemic treatment of metastatic melanoma with IFN-alpha.
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PMID:Effects of systemic interferon-alpha (IFN-alpha) on the antigenic phenotype of melanoma metastases. EORTC melanoma group cooperative study No. 18852. 810 70

Immunohistochemical staining with monoclonal antibodies detected ICAM-1 in about 69% of 55 primary melanoma lesions and in about 89% of 28 metastatic lesions. The average number of melanoma cells stained by anti-ICAM-1 monoclonal antibodies was approximately 65% in both primary and metastatic lesions. ICAM-1 expression in primary lesions was significantly associated with their thickness. Furthermore, ICAM-1 expression in primary lesions was associated with a reduction in the disease-free interval and with survival. At variance with the information in the literature, the association with clinical parameters of the disease did not reach the level of statistical significance. This discrepancy is likely to reflect the inclusion in the present study of a small number of primary lesions with a thickness < 1.5 mm. At variance with recently published data, the level of serum ICAM-1 in 75 patients with malignant melanoma was found to be nonsignificantly different from that in 47 age- and sex-matched controls. The level of serum ICAM-1 was significantly increased only in patients with stage III melanoma with lesions and in those with stage IV melanoma. Two novel and clinically relevant findings of the present investigation are (a) the significantly higher serum ICAM-1 level in patients with liver metastases than in those with metastases in other anatomic sites and (b) the progressive increase of ICAM-1 level in serial blood samples from patients with disease progression. The latter findings suggest that monitoring of serum ICAM-1 level may represent a valuable noninvasive indicator system to detect liver metastases and to monitor the clinical course of the disease in patients with malignant melanoma.
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PMID:Clinical relevance of ICAM-1 expression in primary lesions and serum of patients with malignant melanoma. 810 88

The role of the cell adhesion molecules, LFA-1 and ICAM-1, in intraocular tumor rejection was examined using four different syngeneic intraocular regressor tumors and four different inbred mouse strains. All four tumors undergo T cell-dependent immune rejection in the syngeneic host. Two of the tumors, D5.1G4 melanoma and P91 mastocytoma, undergo rejection by a cytotoxic T lymphocyte-like immune process. The other two tumors, UV5C25 fibrosarcoma and 124E2 melanoma, are rejected by a process that appears to be mediated by delayed-type hypersensitivity. Systemic administration of anti-LFA-1 prevented the rejection of all four categories of tumors. By contrast, similar in vivo treatment with anti-ICAM-1 antibody did not inhibit tumor rejection. The effect of anti-LFA-1 and anti-ICAM-1 antibody treatment on the rejection of metastases arising from intraocular P91 tumors was also examined and found to be highly dependent upon normal LFA-1 function since antibody treatment with anti-LFA-1 prevented the rejection of metastases. Treatment with anti-ICAM-1 antibody alone had no appreciable effect on the rejection of metastases. The results from this study indicate that the expression and function of LFA-1 is crucial for the generation of immune responses to tumor antigens originating within the eye and the expression of tumor immunity within the eye and at distant sites.
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PMID:Anti-leukocyte function-1 antibody treatment prevents the rejection of intraocular regressor tumors and their metastases. 852 8

Angiogenesis is the formation of new capillaries from the existing vascular network and is essential for tumor growth and metastases. Increased microvessel density in breast cancer is associated with lymph node metastasis and reduced survival. We have assessed tumor vascularity in 211 breast carcinomas using a more rapid technique based on a Chalkley point eyepiece graticule. We confirmed using this method a significant reduction in overall survival between patients stratified by Chalkley count in both a univariate (p = 0.02) and multivariate (p = 0.05) analysis. Since studies have suggested that cell adhesion molecules (CAMs) might be important in the angiogenic process, and interaction of neoplastic cells with this neovasculature is a significant step in tumor metastasis, we have also examined the expression of CAMs in a subset of these tumors (n = 64). Using immunohistochemistry we observed widespread and intense staining on the endothelium of tumor-associated vessels for PECAM (100%), ICAM 1 (69%), and E- and P-selectins (52% and 59% of cases respectively). Endothelial expression of the selectins was more prominent at the tumor periphery. Immunoreactivity of ICAM-1 (34%), PECAM (1.6%), and E- and P-selectins (7% and 37% of cases respectively) was also observed on the neoplastic element of the tumors.
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PMID:The prognostic value of quantitative angiogenesis in breast cancer and role of adhesion molecule expression in tumor endothelium. 853 69

Expression of the cell adhesion molecules ICAM-1 (CD54) and LFA-3 (CD58) was examined on primary gastric carcinomas, autologous benign mucosa and metastatic lesions. Although ICAM-1 was never observed on benign gastric epithelium, even in the presence of chronic inflammation and a strong leukocyte infiltrate, 38% (26/69) of the primary tumors expressed this molecule. ICAM-1 was restricted to differentiated tumors and correlated with the presence of leukocytes and the absence of vessel invasion. The ICAM-1 expression pattern of metastatic lesions reflected that of the primary tumor, suggesting that most tumors retain the non-inducible phenotype seen in normal mucosa while some become cytokine-sensitive. ICAM-1 expression showed no correlation with tumor relapse or survival. LFA-3 was absent from 8% (4/49) of the primary tumors and reduced (e.g., < or = 50% positive cells) in 33% (16/49). Expression of LFA-3 by more than 50% of the tumor cells correlated with cellular dedifferentiation (G3, G4), histologically detectable vessel invasion, tumor recurrence and decreased survival time. Primary tumors and metastases in draining lymph nodes demonstrated a broad range of LFA-3 expression. In contrast, distant metastases (liver and peritoneum) had uniformly high frequencies of LFA-3-positive cells, suggesting a selective advantage for these cells in the establishment of distant metastases.
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PMID:Expression of leukocyte cell adhesion molecules on gastric carcinomas: possible involvement of LFA-3 expression in the development of distant metastases. 855 Feb 44

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

Anti-intercellular adhesion molecule-1 (anti-ICAM-1) and anti-lymphocyte-function-associated antigen-1 (anti-LFA-1) monoclonal antibodies (mAbs) were injected into mice and their effects on tumor metastasis were investigated using two murine models. Depending on the dose, the anti-ICAM-1 mAb (KAT-1) expressed both inhibitory and promoting effects on liver metastases of ICAM-1 + LFA-1 + P815 mastocytoma cells, whereas it enhanced lung metastases of the ICAM-1-LFA-1-Meth-A fibrosarcoma cells at any doses. In contrast, anti-LFA-1 mAb (KBA) showed promoting effects only on the metastases of both tumor lines. Treatment of mice with either mAb enhanced metastases of P815 mastocytoma cells in the spleen.
Invasion Metastasis 1996
PMID:Effects of anti-intercellular adhesion molecule-1 and anti-lymphocyte-function-associated antigen-1 monoclonal antibodies on the metastasis of murine tumors. 883 Jul 64

The metastatic process is characterized by a complex series of sequential steps involving constant interactions (mutual "cross-talks") of metastasized tumor cells with their microenvironment (lymphocyte, macrophages, endothelial cells, etc.) in target organs. These interactions determine the outcome of metastasis (either the eradication of metastatic cells or their increased proliferation and invasion). Recently developed methods of tumor and host cell analysis at the molecular level allow better elucidation of molecular mechanisms of metastasis and of immune mechanisms involved in antitumor responses. Direct modulation of these processes will probably increase the success of clinical cancer treatment. Here we review data (a) on the expression of some costimulatory (MHC class II, CD80, sialoadhesin) and adhesion (LFA-1, ICAM-1, VLA-4) molecules on both metastasized tumor cells and host cells and (b) on the production of a cytotoxic molecule, nitric oxide, by in situ activated Kupffer and endothelial cells in the process of liver metastasis. This study was performed with well-characterized murine ESbL T lymphoma cells transduced with the bacterial lacZ gene, which allows detection and quantification of metastases at the single cell level throughout lymphoma growth and metastasis. Experimental results are discussed in the context of recent literature.
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PMID:New insights into tumor-host interactions in lymphoma metastasis. 884 48

Hepatoblastoma is an embryonal tumour of the liver, which often contains tissue components with multidirectional differentiation. The occurrence of cell surface antigens in this tumour has not been studied systematically, and we therefore investigated 20 hepatoblastomas for the expression of common acute lymphoblastic leukaemia antigen (CALLA) and cell adhesion molecules (CAMs) in their different tissue components. Epithelial tumour cells of fetal differentiation contained E-cadherin. This protein did not occur in tumour areas with embryonal or mesenchymal differentiation. In contrast, immature embryonal and anaplastic cells expressed CALLA and the hyaluronate receptor (HCAM, CD44). Both fetal and embryonal areas stained irregularly positive for ICAM-1, which, in contrast, was not present on anaplastic cells. Immature fibrous tissue did not contain any of these molecules except for ICAM-1. However, some cells adjacent to, or enclosed in, osteoid were positive for HCAM and NCAM. Like small undifferentiated hepatoblastoma cells, primitive mesenchymal spindle-shaped cells also expressed CALLA, HCAM, and the polysialylated embryonic form of NCAM strongly. This last is not present on other epithelial or mesenchymal tumour cells. Hepatoblastoma cells of varying differentiation express distinct patterns of CAMs and CALLA. Our results give further insight into their histogenesis and cellular interactions and may explain their variable ability for invasive growth and formation of metastases.
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PMID:Expression of cell adhesion molecules and common acute lymphoblastic leukaemia antigen in hepatoblastoma. 897 59


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