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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 necrosis factor (TNF-alpha) was compared to immune interferon (IFN-gamma) for its ability to modulate the expression and shedding of HLA antigens, of intercellular adhesion molecule I (ICAM I) and of high-molecular-weight melanoma-associated antigen (HMW MAA) by a panel of melanoma cell lines. The latter included the melanoma cell line MeWo and its metastatic variant MeM 50-10, which display differential susceptibility to modulation of HLA class-II antigens by IFN-gamma and the cell lines SK-MEL-93-DX-2 and SK-MEL-93-DX-3, which originated from anatomically distinct metastases in patient DX. TNF-alpha enhanced the expression of HLA class-I antigens on all 7 melanoma cell lines tested, although to a lower extent than IFN-gamma and the combination of IFN-gamma and TNF-alpha. TNF-alpha displayed a differential effect on the expression of HLA class-II antigens by the 7 melanoma cell lines: it enhanced it on 3 out of the 4 cell lines with constitutive expression of HLA class-II antigens and induced them on 1 of 3 cell lines without detectable expression of these antigens. The effects of IFN-gamma were different since it enhanced HLA class-II antigens on the 4 cell lines with constitutive expression of these antigens and induced them on 2 out of the remaining 3 lines. Interestingly, both TNF-alpha and IFN-gamma enhanced the expression of HLA class-II antigens by SK-MEL-93-DX-3 cells. On the other hand only TNF-alpha induced the expression of HLA class-II antigens by MeWo cells and only IFN-gamma induced such expression by MeM 50-10 cells and by SK-MEL-93-DX-2 cells. The effect of the combination of TNF-alpha and IFN-gamma was similar to that of the individual cytokines. Both TNF-alpha and IFN-gamma displayed a differential effect on the expression of the gene products of the HLA-D region by the melanoma cell lines. Northern blot analysis with HLA-DR beta-, DQ beta- and DP beta-specific probes suggests that the modulation of HLA class-II antigens by both cytokines reflects transcriptional and post-transcriptional events. TNF-alpha enhanced the expression of ICAM-I on all the melanoma cell lines, although to a lower extent than IFN-gamma and the combination of IFN-gamma and TNF-alpha. Lastly, neither TNF-alpha nor IFN-gamma displayed a marked effect on the expression of HMW-MAA by the melanoma cell lines tested.
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PMID:Differential modulation by tumor necrosis factor and immune interferon of HLA class-II antigens expressed by melanoma cells. 250 38

As discussed in the preceding sections, there are several indications that the lymphocyte homing receptors involved in the normal process of lymphocyte recirculation are also relevant to the behavior of metastatic cells. Cell fusion experiments indicate that previously nonmetastatic cells can acquire metastatic capacity from fusion with normal lymphocytes. Murine T lymphomas that bear high levels of functional homing receptors can metastasize to peripheral lymphoid organs, whereas those lymphomas lacking homing receptors cannot. Virtually all lymph node metastases of lymphomas contain a high proportion of MEL-14hi cells, even if the primary tumor has been selected to be relatively deficient in these cells. Further investigations of the biology of lymphocyte homing receptors will reveal whether or not there are additional lymphocyte homing receptors and will clarify the role of lymphocyte homing receptors in metastasis. Antibodies against three lymphocyte homing receptors could therefore be useful for diagnosis and treatment of metastatic disease.
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PMID:Homing receptors and metastasis. 306 47

We conducted a trial of a murine monoclonal antimelanoma antibody-ricin A chain immunotoxin (XOMAZYME-MEL) in 22 patients with metastatic malignant melanoma. The dose of immunotoxin administered ranged from 0.01 mg/kg daily for 5 days to 1 mg/kg daily for 4 days (total dose: 3.2 to 300 mg). Side effects observed in most patients were a transient fall in serum albumin with an associated fall in serum protein, weight gain, and fluid shifts resulting in edema. In addition, patients experienced mild to moderate malaise, fatigue, myalgia, decrease in appetite, and fevers. There was a transient decrease in voltage on electrocardiograms without clinical symptoms, change in serial echocardiograms or elevation of creatine phosphokinase MB isozyme levels. Symptoms consistent with mild allergic reactions were observed in three patients. The side effects were related to the dose of immunotoxin administered and were generally transient and reversible. Encouraging clinical results were observed, even after a single course of a low dose of immunotoxin. In addition, localization of antibody and A chain to sites of metastatic disease was demonstrated by immunoperoxidase staining of biopsy specimens. Additional studies are being conducted to continue the evaluation of safety and efficacy of immunotoxin therapy for malignancy.
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PMID:Therapy of patients with malignant melanoma using a monoclonal antimelanoma antibody-ricin A chain immunotoxin. 349 66

The immunohistochemical reactivity of the monoclonal antimelanoma antibody MEL-1 was evaluated on frozen sections of 9 malignant melanomas, 5 nevi, 1 squamous cell carcinoma, 1 basal cell carcinoma, 2 benign dermal fibrous histiocytomas, 1 infiltrating ductal and 2 infiltrating lobular carcinomas of the breast, 1 primary squamous cell carcinoma and 1 adenocarcinoma of the lung, 1 lung metastasis of gastric adenocarcinoma, 1 adenocarcinoma of the large bowel, 1 lymph node, 1 case of malignant histiocytosis and one of lymph nodal immunoblastic lymphoma, and 1 biopsy of oral cavity mucosa. In primary and metastatic malignant melanoma, junctional nevi, and the upper half of compound and dermal nevi, the staining was intense. Also, benign dermal fibrous histiocytoma and the case of lymph nodal malignant histiocytosis showed an intense reactivity, whereas the immunostaining positivity of the squamous cell carcinoma of the skin, the lung adenocarcinoma, the squamous cutaneous and mucosal epithelium, and the sweat and sebaceous glands was slight. In ductal and lobular infiltrating carcinoma of the breast only focal areas or isolated tumor cells were positive. The lack of reactivity of deep dermal melanocytes of compound and dermal nevi may be correlated with a different antigenic phenotype of the melanocytes. After discussion of the technical problems, the application of MEL-1 was suggested, for diagnostic purpose, to identify lymph nodal metastases in cases of primary self regressed malignant melanoma and to detect lymph nodal metastatic microfoci of malignant melanoma.
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PMID:Immunohistochemical reactivity of the antimelanoma monoclonal antibody MEL-1. 389 83

Two human melanoma cell lines, derived from metastases of two patients with epithelioid malignant amelanotic melanomas, and designated IIB-MEL-LES and IIB-MEL-IAN, have been established. Both cell lines have been in continuous culture over 2 years and were propagated continuously for 85 and 75 serial passages, respectively. Morphologically, IIB-MEL-LES is composed predominantly of spindle shaped cells, whereas IIB-MEL-IAN grows as a monolayer of cuboid and stellate shaped cells with many rounded cells in suspension. Immunocytochemical studies revealed that both cell lines express S-100 protein, vimentin, and GD3 and GD2 gangliosides but are negative for keratin and collagen. Both cell lines express HLA class I and HLA-DR antigens in variable proportions. The MAGE-1 gene is expressed only by the IIB-MEL-IAN cell line, as revealed by PCR analysis. Cytogenetic analysis of both cell lines revealed abnormal karyotypes; the modal chromosome numbers of IIB-MEL-LES and IIB-MEL-IAN were 48 and 81, respectively. IIB-MEL-LES cells presented rearrangements in chromosomes 1, 14 and X, gains in chromosomes 10, 20, and 21 losses in chromosomes 15 and Y. The most frequent markers observed in IIB-MEL-IAN cells were 7q+, 10p+, 2p+, i(6p), 2q+, and 10q-. Clonal gains were observed in chromosomes 12 and 21, whereas losses were seen in chromosomes 1, 2, 3, 4, 6, 7, 11, and 17. Both cell lines were capable of forming colonies in soft agar and developed tumors when transplanted into nude mice, reproducing and maintaining the characteristics of the original tumors. These cell lines and their xenografts appear to provide useful systems for studying the biology, genetics and histogenesis of human malignant melanoma and could be utilized for the development of melanoma vaccines.
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PMID:Biologic, immunocytochemical, and cytogenetic characterization of two new human melanoma cell lines: IIB-MEL-LES and IIB-MEL-IAN. 756 87

The regional chemotherapy of the human malignant melanomas (SK-MEL-2, -3, -5, -24) implanted in NMRI nu/nu mice with a combination of the hyaluronic-acid-cleaving enzyme hyaluronidase (HYase) and vinblastine is a very effective therapeutic procedure. In three out of four melanoma models (SK-MEL-2, -3, -5) the weekly peritumoral administration of high-dose HYase (100,000 IU/kg) 4 h prior to the injection of 0.3 mg/kg vinblastine in the vicinity of the tumor (seven weekly therapeutic cycles) caused marked antitumor effects, while HYase and vinblastine were inactive when given alone. The pretreatment with HYase, which is well tolerated by the test animals, prevented local inflammation reactions commonly seen after subcutaneous vinblastine administration. Tumor growth and metastatic behavior of the melanomas used were neither increased nor reduced by HYase after peritumoral administration without subsequent vinblastine injection. The curative activity of the regional chemotherapy with HYase/vinblastine could be demonstrated on the SK-Mel-3 melanoma. After an observation time of 18 weeks, tumor cells could no longer be detected in the subcutaneous region of the former lesion. Only macrophages, which had abundantly incorporated melanin, gave evidence of previously growing tumors. In contrast to the controls, no metastases could be observed in the axillary lymph nodes of the test animals.
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PMID:Hyaluronidase significantly enhances the efficacy of regional vinblastine chemotherapy of malignant melanoma. 775 17

We have studied the patterns of antigens recognized by autologous cytolytic T lymphocytes (CTL) on two melanoma cell lines derived from metastases that were removed from patient LB33 at several years distance. Cell line LB33-MEL.A was obtained after surgery in 1988. A large number of CTL clones directed against LB33-MEL.A was obtained with blood lymphocytes collected from the patient in 1990. In vitro selection of melanoma cells that were resistant to these CTL clones indicated that at least five different antigens were recognized on LB33-MEL.A by autologous CTL. Four of these antigens were found to be presented by HLA-A28, B13, B44 and Cw6, respectively. The patient remained disease-free until 1993 when a metastasis was detected and was used to obtain cell line LB33-MEL.B. This cell line proved resistant to lysis by all the CTL clones directed against the LB33-MEL.A cells and showed no expression of HLA class I molecules except for HLA-A24. Using LB33-MEL.B cells to stimulate blood lymphocytes collected from the patient in 1994 we derived CTL clones that lysed these cells. All these CTL clones recognized a new antigen presented by HLA-A24. These results suggest that in patient LB33 the melanoma cells may have lost the expression of several HLA molecules under the selective pressure of an anti-tumor CTL response.
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PMID:Differences in the antigens recognized by cytolytic T cells on two successive metastases of a melanoma patient are consistent with immune selection. 787 94

Surface expression of human leukocyte antigen (HLA) class I antigens on melanoma lines was evaluated by locus-specific monoclonal antibodies (mAbs) with three different techniques: Fluorescence-activated cell sorting (FACS), immunohistochemistry with cytospin preparation (ICP), and complement-mediated cytotoxicity (CMC). Eleven HLA class I-expressing cell lines developed from metastases were used. Specific expression of HLA loci was examined under routine culture conditions and after 48-h incubation in interferon-gamma (IFN-gamma; 500 U/ml). Loss of allelic expression was seen in one line (586-MEL): Products of genes coding for HLA-A29 and -B44, in strong linkage disequilibrium, were not detectable. HLA-A antigens were consistently detected by all methodologies and minimally affected by pretreatment with IFN-gamma. HLA-B antigens were detectable in 8 of 11 lines by ICP and 3 of 11 lines by CMC. By FACS the supratypic specificity HLA-Bw6 was expressed at low levels in most lines (mean fluorescence 47.2 +/- 13.4 and rose to 259.8 +/- 45.9 after incubation with IFN-gamma; p < 0.001). HLA-Cw antigen detection by CMC correlated with HLA-B (p < 0.01), suggesting that down-regulation and sensitivity to IFN-gamma are shared by the two loci. This low expression of the HLA-B antigens may play a role in the evasion of the host immune response and its up-regulation may be useful in allowing tumor antigen recognition.
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PMID:Locus-specific analysis of human leukocyte antigen class I expression in melanoma cell lines. 808 56

Twelve human melanoma cell lines were analyzed for alterations in the epidermal growth factor receptor (EGFR) gene at the DNA, RNA and protein levels. EGFR expression of the cell lines was then correlated with their previously reported p53 expression, in vivo growth characteristics, and rate of metastases in athymic mice. Northern blot and immunocytochemical analyses demonstrated low to intermediate levels of EGF receptor expression in four cell lines. Overexpression of EGFR was seen in one cell line, UISO-MEL-6. Although no significant statistical difference was observed between in vivo growth of EGFR-positive cell lines versus EGFR-negative cell lines, UISO MEL-6 which also lacked p53 expression, had the fastest in vivo rate of growth and was the only cell line to produce visceral metastases following subcutaneous inoculation in nude mice. Furthermore, EGFR overexpression in UISO-MEL-6 was associated with alterations of the gene at the DNA level.
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PMID:Overexpression of EGF receptor is associated with spontaneous metastases of a human melanoma cell line in nude mice. 904 21


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