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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, many surface proteins of lymphoid cells that mediate adhesion to other cells and extracellular matrix have been identified. Several of these cellular adhesion molecules (CAM) are also expressed by metastatic lymphoma cells and may mediate adhesion to tissue components during the metastatic process. Correlations observed between expression of certain CAM, like MEL-14 and CD44, and particular patterns of spread, support this notion, but conclusive evidence is scarce. We have used T-cell hybridomas to study the mechanisms of wide-spread lymphoid metastasis. The results obtained with this model are reviewed here. The advantages are that a large number of genetically similar cell lines can be generated, which can be grouped in large panels of highly invasive and non-invasive cells. Invasiveness of these cells in hepatocyte and fibroblast monolayers correlates with experimental metastasis. Lymphoid CAM that are potentially involved in metastasis are reviewed. Several of these CAM are not, or not consistently, expressed by the invasive T-cell hybridomas, indicating that they are not indispensable. Notably, some of the CAM involved in the onset of an immune response or in migration into inflamed tissues, like ICAM-1 and VLA-4, and the 'homing receptors' MEL-14 and LPAM-1 do not seem to be involved. CAM that are consistently expressed by the T-cell hybrids include LFA-1, the beta-1 integrin subunit CD29, CD31 (PECAM-1) and CD44 ('Hermes homing receptor'). We have generated considerable evidence that LFA-1 is required for efficient metastasis of T-cell hybrids, based on the behavior of LFA-1-deficient mutants and revertants. High levels of LFA-1 are required. The relevant counterstructure is probably ICAM-2 rather than ICAM-1. Preliminary results suggest that also a beta-1 integrin, possibly VLA-5, plays a role. Finally, we summarize evidence indicating that CD31 and CD44 are primary candidates for involvement in metastatic spread of T-cell hybridomas.
Cancer Metastasis Rev 1991 May
PMID:Adhesion molecules in lymphoma metastasis. 168 May 76

Tumor cell variants were derived from an AKR T-cell lymphoma cell line (BW5147, H-2k haplotype). These variants differed in their malignant potential and in their membrane expression of class I MHC antigens. High tumorigenic and spontaneous metastatic capacity was found to be predominantly associated with a decrease of H-2Kk class I major histocompatibility complex (MHC) antigen expression. In contrast, high experimental metastatic capacity correlated strongly with an increased H-2Dk antigen expression. The in vitro invasive potential and the LFA-1 expression of the BW variants showed no correlation with the differential MHC antigen expression and the differential metastatic and tumorigenic capacity of the BW variants. Furthermore, the susceptibility of the BW 5147 variants to TNF and NK-mediated cytotoxicity was not related to the differential metastatic potential and the expression of the class I MHC antigens.
Invasion Metastasis 1990
PMID:Association between MHC class I antigen expression and malignancy of murine T lymphoma variants. 230 62

Identification of antigens by monoclonal antibodies (MAbs) on sections of human melanoma by immunoperoxidase techniques was used to determine whether certain adhesion molecules and "selectin-like" molecules may be related to the metastatic potential of primary melanoma. The adhesion molecules examined were the leukocyte function antigen (LFA-1) and its ligand--intercellular adhesion molecule-1 (ICAM-1), the receptor alpha V beta 3 for vitronectin, its subunits alpha V and beta 3, and the CD36 receptor for thrombospondin (TSP). The criteria used to establish metastatic potential were relation of the molecules to tumor thickness and differences in expression: (i) between radial and vertical growth phases of the primary tumors and (ii) between 34 primary and 21 unrelated metastases. By these criteria ICAM-1, alpha V beta 3 and its subunit were associated with the malignant potential of primary melanoma. These molecules were not expressed on nevi or other skin cancers with low metastatic potential such as squamous (SCC) and basal cell carcinomas (BCC). In contrast, expression of TSP and the CD36 receptor for TSP were not related to metastatic potential. CD36 was expressed widely not only on melanoma but also on BCC, SCC and nevi. Similarly, the selectin-like molecule, CD44, was widely expressed on melanoma and non-melanoma carcinomas. The lymph node homing receptor, Leu 8, and the cutaneous lymphocyte antigen (CLA) were not detected on melanoma. Leu 8 was present on normal epithelium and SCCs, and common leucocyte antigen (CLA) was detected on lymphocytes in the epithelium and near melanoma. These results support previous suggestions that expression of ICAM-1 and V beta 3 integrin or its subunit beta 3 on melanoma may be a useful prognostic marker in primary melanoma. They do not support a role for CD44, Leu 8, CLA and TSP or its receptor CD36 in the metastatic process in melanoma.
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PMID:Immunohistological examination of the relationship between metastatic potential and expression of adhesion molecules and 'selectins' on melanoma cells. 751 76

An overview is presented of our studies on the interaction between blood-borne tumor cells and the tissues where metastases are formed, in particular the liver. Using blocking antibodies and tumor cell mutants, we have identified the adhesion molecules involved, which so far are all integrins. Strikingly, tumor cell lines that are quite similar, and invade in a comparable fashion, use distinct integrins. Lymphomas that invade the liver massively and diffusely use LFA-1 or fibronectin receptors to adhere to hepatocytes. We have obtained evidence that LFA-1 is activated during the interaction by factors that act through G-protein-coupled receptors, and preliminary results suggest that the same may be true for the fibronectin receptors. Whereas TA3/Ha murine mammary carcinoma cells adhere to hepatocytes via alpha 6 beta 4, TA3/St variant cells of the same tumor bind via the fibronectin receptor alpha 5 beta 1. Adhesion of the TA3/Ha cells appears to be impaired by the mucin epiglycanin that is abundantly present on the surface of these cells.
Invasion Metastasis
PMID:The role of integrins and integrin activation in liver metastasis. 765 36

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

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

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

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

T-cell hybridomas metastasize widely, and the extent of dissemination correlates with invasiveness in fibroblast cultures. Previously, we provided evidence that both metastasis and in vitro invasion require activation of LFA-1, induced by G-protein-transduced signals triggered by as yet unidentified factors. We show here that LFA-1-mediated adhesion of TAM2D2 T-cell hybridoma cells to ICAM-1 can in fact be induced by direct activation of G-proteins using AIF-4, to the same extent as by using PMA or Mn2+. We assessed effects of protein kinase C (PKC), tyrosine kinase (TK), PI3-kinase (PI3K), and phospholipase C (PLC) inhibitors. Both AIF-4-induced adhesion and invasion were completely blocked by the TK inhibitor genistein and partially blocked by the PI3K inhibitor wortmannin, but not influenced by PKC inhibitor GF109203X. Downregulation of PKC did not affect invasion or adhesion induced by AIF-4 either. In contrast, GF109203X and PKC downregulation blocked PMA-induced adhesion, but genistein and wortmannin had no effect. Invasion and both AIF-4- and PMA-induced adhesion were completely blocked by the PLC inhibitor U73122. Mn(2+)-induced adhesion, which was not or was only partially blocked by the other inhibitors, was delayed by U73122, and spreading of Mn(2+)-treated cells was completely prevented by U73122. However, PLC activity during adhesion was not detected. We conclude that signals required for invasion and G-protein-induced adhesion are similar and are distinct from PKC-induced adhesion, and that in all cases PLC is likely to be activated, but is probably too local and/or transient to be detected.
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PMID:Activation of G-proteins with AIF-4 induces LFA-1-mediated adhesion of T-cell hybridoma cells to ICAM-1 by signal pathways that differ from phorbol ester- and manganese-induced adhesion. 908 64


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