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)

To identify molecules which may be functionally associated with the development of metastasis in human melanoma, monoclonal antibodies which discriminate between benign and malignant melanocytic lesions in situ were selected. Biochemical studies and cDNA cloning identified the antigens HLA-DR, ICAM-1 and MUC18 which showed an expression pattern on primary tumors correlating with vertical tumor thickness, the most predictive parameter for the development of metastasis in melanoma. ICAM-1 and MUC18 show sequence similarity to a family of cell adhesion molecules which include the neural cell adhesion molecule NCAM. Both HLA-DR and ICAM-1 can be induced on melanoma cells by lymphokines, suggesting a role of the mononuclear cell infiltrate in the control of tumor cell phenotype. Knowledge of the normal function of these molecules allows one to hypothesize how they may contribute to the successful development of metastases.
Invasion Metastasis 1989
PMID:Functional aspects of three molecules associated with metastasis development in human malignant melanoma. 257 17

The CD44 molecule and CD44 isoforms are expressed on some malignant tumours and it has been suggested that their expression may correlate with tumour spread. Human pancreatic carcinoma cell line (HPC-4) expressing CD44 was established from a patient with adenocarcinoma of pancreas. This line showed a rapid growth in vitro, several chromosome abnormalities and surface expression of some adhesion molecules (ICAM-1, LFA-3, beta 1-chain of VLA integrins, VNR). Xenotransplanted HPC-4 cells were able to grow rapidly in SCID mice as subcutaneous tumour, leading to 100% mortality within 3-5 weeks when 1 x 10(5)-1 x 10(7) cells were inoculated. Spontaneous metastases in the liver, lung, spleen and kidney of SCID mice were observed. Interestingly enough, HPC-4 cells in vivo and ex vivo also expressed HLA-DR molecules, but these were rapidly lost upon culture in vitro. It is suggested that the appearance of HLA-DR may be the result of interaction of the tumour with a local environment of the host, while CD44 expression may explain the rapid growth and occurrence of distant metastases in SCID mice. The ability of HPC-4 cells to form spontaneous metastases in SCID mice may prove to be a potentially interesting model of human carcinoma for testing new treatment modalities.
Invasion Metastasis 1995
PMID:Characterization of human pancreatic adenocarcinoma cell line with high metastatic potential in SCID mice. 754 54

Loss and gain of cell surface molecules determines the mobilization, emigration and invasiveness of epithelial cancer cells. As a first approach to gain further insight into these processes, we have followed two strategies: (1) to identify tumour cells which have disseminated early from primary carcinomas and to obtain information about the phenotype and prognostic significance of these cells; and (2) to identify molecular changes occurring in primary tumour cells at the time they develop their metastatic potential. Our analyses indicate that changes in the adhesive properties of solid tumour cells, such as down-regulation of desmosomal proteins (e.g. plakoglobin) and neo-expression of ICAM-1 or MUC18, are important determinants of the metastatic capability of individual malignant cells. The expression pattern of these cell adhesion molecules during tumour progression appears to reflect a disturbance at the level of the molecular elements normally responsible for controlling their expression. The outlined current strategies for detection, characterization and antibody therapy of cancer micrometastasis can be applied to the secondary prevention of metastatic disease in patients with minimal residual cancer.
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PMID:Early metastasis of human solid tumours: expression of cell adhesion molecules. 758 30

The past decade has witnessed substantial progress in our understanding of the molecular mechanisms of tumor cell interactions with vascular endothelium and extracellular matrix, important events in the metastatic process. This progress has been made possible by the identification and functional characterization of a large number of adhesion molecules involved in tumor cell-vasculature interactions. Essentially, most of the adhesion receptor families so far reported, including integrins, cadherins, selectins, immunoglobulins, and proteoglycans, have been implicated in various stages of tumor progression and metastasis. Disseminating cancer cells often employ ectopic expression of certain adhesion molecules to facilitate their interaction with the vessel wall and matrix, typical examples being the expression of integrins alpha IIb beta 3 and alpha L beta 2 and immunoglobulin family members PECAM-1, ICAM-1, and N-CAM in solid tumor cells. The expression of adhesion molecules in cancer cells and vascular endothelial cells is spatiotemporally regulated, in a dynamic fashion, by a wide diversity of bioactive molecules such as eicosanoid 12(S)-HETE. Recent data indicate that most adhesion molecules, integrins in particular, participate in various signaling functions such as the induction of calcium fluctuation and protein tyrosine phosphorylation. The importance of adhesion molecules in tumor metastasis is also evidenced by their involvement in other important parameters of metastasis such as angiogenesis. Collectively, the accumulated literature suggests that interference with adhesion and signaling represent a future direction for the development of anticancer and antimetastasis therapeutic protocols.
Invasion Metastasis
PMID:Adhesion molecules and tumor metastasis: an update. 765 6

Differential antibody reactivity has been used to identify molecules which change in expression or which are modified during tumor progression in human malignant melanoma. Such molecules may play a role in the development of the metastatic capacity of this tumor. Two of these molecules (ICAM-1 and MUC18) have been identified as cell adhesion molecules which are potentially involved in tumor-leukocyte-endothelial interactions.
Invasion Metastasis
PMID:Identification of molecules associated with the development of metastasis in human malignant melanoma. 765 7

Knowledge about transcription factors is crucial for understanding the molecular basis of neoplasia. Homeobox-containing genes are a family of transcription factors mostly involved in normal development. Class I human homeobox-containing genes (HOX genes) are organized in four clusters on different chromosomes. The order of the genes within each cluster is highly conserved throughout evolution suggesting that the physical organization of HOX genes may be (1) essential for their expression and (2) responsible for major biological functions. We have studied HOX gene expression in several human tissues and organs as well as in their neoplastic counterparts. We have observed (a) characteristic patterns of HOX gene expression for each normal solid organ analyzed, (b) altered HOX gene expression in kidney and colon cancer, (c) a correlation between HOX gene expression and different histological types of primary small cell lung cancer (SCLC) and (d) marked alterations of HOX gene expression among primary and metastatic SCLC variant types. Furthermore, we have shown that differential patterns of HOX gene expression correlate with the adhesion profile (VLA-2, VLA-5, VLA-6 and ICAM-1) and N-RAS mutation in clonal melanoma populations isolated from a single human melanoma metastasis. This suggests that HOX genes act as a network of transcriptional regulators involved in the process of cell to cell communication during normal morphogenesis, the alteration of which may contribute to the evolution of cancer.
Invasion Metastasis
PMID:HOX genes in human cancers. 765 31

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

Intercellular adhesion molecule-1 (ICAM-1) is the natural ligand of the T-lymphocyte adhesion molecule LFA-1 (lymphocyte-function-associated antigen-1). ICAM-1 is involved in target cell recognition by T-lymphocytes, LAK cells and natural killer cells. The molecule has also been detected on a variety of normal cells and on human tumors. Renal cell carcinoma (RCC) is one of the few tumors that respond to immunotherapy, but clinical results are generally disappointing. We therefore analyzed, by immunohistochemistry, the expression of ICAM-1 in pairs of normal kidneys, RCC, and RCC metastases. Moreover, serum ICAM-1 was determined in RCC patients and compared with surface expression of cell-bound ICAM-1. Strong glomerular expression of ICAM-1 was observed in all specimens of normal kidney examined. Proximal tubuli were weakly stained in the majority of specimens. Of the tumors, 80% stained positive for ICAM-1. Although ICAM-1 was detected on the majority of extrarenal tumor specimens examined, staining was generally weaker in the metastases. Patients without metastases at initial presentation more frequently expressed ICAM-1 in their primary tumors than did patients with metastases. Levels of serum ICAM-1 (sICAM-1) were significantly higher in RCC patients than in controls with non-malignant renal diseases. Patients with an unfavorable prognosis, e.g. with advanced tumor stage or metastasis at initial presentation, had higher levels of sICAM-1 than patients with low-grade and/or low-stage tumors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cell surface expression and serum levels of intercellular adhesion molecule-1 in renal cell carcinoma. 791 44

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

We previously reported that a derivative of the interleukin-6 (IL-6)-dependent B9 B-cell hybridoma (B9/LPNU1L) constitutively expressing an interleukin-1 alpha (IL-1 alpha) gene introduced by retrovirus-mediated gene transfer preferentially metastasized to bone marrow following intravenous injection into unirradiated syngeneic BALB/c mice. B9/LPNU1L cells recovered from the femoral marrow of a recipient with hind limb paralysis (denoted B9/BM1) retained their IL-6-dependency yet displayed enhanced metastatic capacity during serial transplantation in vivo. In contrast, autonomously-growing B9 variants spontaneously arising in vitro or IL-6-independent B9 derivatives created by infection with recombinant IL-6 retroviruses rarely gave rise to experimental metastases in syngeneic BALB/c or nude mice. Examination of cell adhesion molecule profiles by immunofluorescence flow cytometry has revealed high levels of CD44, moderate levels of VLA-4 and low levels of LFA-1 on all B9-series cells. By comparison, ICAM-1 expression was significantly elevated on B9/BM1 cells, with independent isolates stably expressing about 4-fold higher levels which were paralleled by corresponding increases in the steady-state levels of ICAM-1 mRNA. L-Selectin was not expressed by any of the cell lines. Despite higher ICAM-1 levels, cell aggregation assays revealed that LFA-1-ICAM-1 adhesive interactions were not involved in the homotypic adhesion of B9/BM1 cells but rather that binding of CD44 to endogenously-synthesized hyaluronan was responsible. Furthermore, B9/BM1 cells expressing high levels of ICAM-1 were found to be less susceptible to cytolysis by natural killer (NK) cells than their weakly metastatic or nonmetastatic counterparts.
Clin Exp Metastasis 1993 Mar
PMID:Association between ICAM-1 expression and metastatic capacity of murine B-cell hybridomas. 809 98


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