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

It has been recently established that there is a correlation between the lack of MHC class I gene expression on murine tumour cells and their ability to grow and metastasize. We have studied the expression of HLA-ABC and HLA-DR products on human malignant tumours from the digestive tract using monoclonal antibodies, by indirect immunofluorescence on the cell suspensions obtained from 29 freshly explanted digestive tumours. Our results show that digestive tract cancers have an heterogeneous expression of HLA class I molecules on their surface. Whereas 50% have high levels of expression of these molecules (more than 60% positive cells), 25% have a moderate level of expression (20-60% positive cells) and 25% have weak expression (less than 20% positive cells). It has been found that there is a correlation between the level of HLA class I molecule expression and the degree of histological differentiation of a tumour. The absence of MHC class I antigens on human tumour cells, detected in this study, may play a relevant role in oncogenesis, as has been established in experimental models.
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PMID:Expression of HLA molecules on cells from fresh explants of human digestive tract cancer. 381 52

Acute leukemia comprises a large group of different diseases that can be identified by morphology in combination with immunological markers. Such studies suggest that phenotypic heterogeneity may be expressed in individual leukemia cell populations. This was verified in the murine AKR leukemia that was found to be composed of four antigenically different subtypes of leukemia cells, and it was shown that this feature has a severe negative impact on the use of leukemia cell specific monoclonal antibodies (Mabs) as therapeutical reagents. Twenty-four human T-lymphoblastic leukemias were analyzed with Mabs against HLA class I, HLA class II, and T-lymphocyte differentiation antigens, and 21 were found to be intratumoral heterogeneous with respect to these antigens. Mabs with high specificity were generated against AML cells and subsequently used to analyze more than 50 AML samples from different patients. The reactivity pattern of the Mabs differed significantly among the various AML samples. Further, a pronounced intratumoral antigenic heterogeneity (IAH) was found in most AML samples with regard to reactivity of the Mabs against AML and expression of major histocompatibility antigens. The negative impact of IAH on the use of Mabs in clinical oncology is described. It is argued that IAH exemplifies the phenotypic diversity of malignant neoplasms which is also suggested to be a basic and necessary feature of malignant cell populations. Mabs against subsets of malignant cell populations may have a profound effect on cancerous cell populations, and it is therefore of crucial importance that such subsets are identified and characterized. It is conceivable that this may result in generation of Mabs with potentially high value in cancer diagnosis and therapy, particularly in combination with drugs that induce differentiation in the malignant cell mass.
Cancer Metastasis Rev 1983
PMID:Phenotypic diversity in leukemia cell populations. 635 12

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

We studied by immunohistochemistry the HLA-allelic, beta 2-microglobulin, and TAP-1 expression in primary breast carcinomas and related lymph node metastases. Thirty-three of the primary tumors and 44% of the lymph node metastases had a complete HLA class I loss. The higher incidence of antigenic loss in metastatic tumors suggests that recognition of HLA class I antigens by the host immunity could have an important role in the metastatic evolution of breast cancer. We observed a simultaneous defective expression of all three components involved in HLA class I expression. Since the controlling genes of heavy chain and TAP-1 are located in different chromosome than beta 2-microglobulin, it could be that a common factor exists regulating HLA class I antigenic expression. Five of 25 (20%) primary and metastatic tumors from HLA-A2-positive individuals also had a selective loss. The high incidence of HLA class I loss in breast cancer patients shows that adjuvant immunotherapy to induce HLA class I expression could be of value in a subgroup of patients.
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PMID:Loss of transporter in antigen processing 1 transport protein and major histocompatibility complex class I molecules in metastatic versus primary breast cancer. 758 72

We have compared the pattern of surface antigen expression, as detected by monoclonal antibodies (mAbs), in plasma membranes vs shed membrane vesicles of two human breast carcinoma cell lines, MCF-7 and 8701-BC. Antigen expression was detected on cells by immunofluorescence (IF) analysis, whilst, due to their small dimensions, the same technique was not applicable to vesicles. For these structures dot-blot analysis and immunoelectron microscopy (IEM) were employed. When applicable, both cell membranes and membrane vesicles were immunoprecipitated and the precipitate (IP) was analyzed by SDS-PAGE. Cells of both lines expressed HLA class I antigens, epithelial cytokeratins, beta 1 integrins, CEA and the glycoprotein detected by mAb 19.9, but only MCF-7 cells expressed Lewis Y, episialin and globo-H antigens and only 8701-BC cells expressed folate receptor. Membrane vesicles of both cell lines appeared to be rich in beta 1, alpha 3 and alpha 5 integrin chains, expressed HLA class I antigens and carried most of the plasma membrane antigens found in the cell membranes. Overall we have analyzed 17 antigens on the two cell lines and on their vesicles. The results obtained for cells (IF and IP) and those for vesicles (dot-blot and IP) were generally concordantly positive or concordantly negative. We obtained a total of 26 clearly concordant combinations on 34 analyses. In three cases we found discordant results, whereas in the remaining combinations we observed slight reactivity and we found difficulties in determining concordance. Discordant results concerned the expression of the following antigens: folate receptors, which were clearly expressed in 8701-BC cells but not detected by dot-blot analysis or IEM on their shed membrane vesicles; neu (c-erb-B2) receptor found in MCF-7 cell membranes but not in their vesicles; and the globo-H antigen recognized by mAb MBr1, detected at low levels on 8701-BC plasma membranes but undetectable on their membrane vesicles. Like vesicles shed in vitro by cultured cells, the vesicles shed in vivo by human breast carcinoma cells could be tagged with several antibodies against tumor-associated antigens. The vesicles shed in vivo were found in association with a fiber network. Some of the fibers had the characteristic fibrin periodicity. These data suggest that tumor markers detected in the circulation of carcinoma patients, at least in part, are carried by shed membrane vesicles. Moreover the observation that membrane vesicles carry both tumor-associated antigens and HLA class I molecules indicate that these structures could in principle present antigens to the immune system.(ABSTRACT TRUNCATED AT 400 WORDS)
Clin Exp Metastasis 1995 Jul
PMID:Membrane vesicles shed into the extracellular medium by human breast carcinoma cells carry tumor-associated surface antigens. 760 90

A correlation between the lack of MHC class I gene expression on murine tumor cells and their ability to grow and metastasize has recently been established. This paper studies HLA-ABC and HLA-DR antigen expression in tumor cells and mononuclear infiltrate of 26 cutaneous squamous cell carcinomas (SCC). Our results showed a heterogeneous expression of HLA class I molecules in these tumors. No significant correlation between the degree of HLA class I molecule expression and anatomical-clinical parameters was found. Class II antigen expression was correlated to the histopathological type and to the degree of cell differentiation. Most mononuclear cells infiltrating the tumor were T-lymphocytes. No correlation with anatomical-clinical parameters was found.
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PMID:HLA molecule expression in cutaneous squamous cell carcinomas: an immunopathological study and clinical-immunohistopathological correlations. 768 37

The altered expression of histocompatibility leukocyte antigens (HLA) in the development to cervical carcinoma suggests that tumor progression may be related to impaired recognition by host immune defense mechanisms. To investigate whether this phenomenon plays a role in the process of metastasis of cervical cancer, we analyzed and compared the HLA expression with the number of infiltrating immune cells in primary cervical carcinoma and related autologous metastases (n = 30) by staining serial paraffin and corresponding frozen sections with a panel of monoclonal antibodies. In 60% of the cervical metastases, compared to 21% of the primary tumors, a downregulation of monomorphic HLA class I antigens was observed, with frequent allele-specific alterations. In 50% the HLA class II expression was slightly increased on the metastatic tumor cells in comparison to the primary tumor. In addition, variability of alterations in HLA expression was observed between different metastases in the same patient. A minor infiltration of immune cells was present in cervical metastases compared to the primary tumors, especially in the HLA class I-downregulated metastases. Furthermore, loss of HLA class I expression on the metastatic tumor cells resulted in a significant decrease of tumor-infiltrating CD8+ T lymphocytes. These findings suggest that in cervical carcinoma loss of HLA class I expression plays a decisive role in the escape from immune surveillance leading to a greater metastatic potential of tumor cells.
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PMID:Altered HLA expression by metastatic cervical carcinoma cells as a factor in impaired immune surveillance. 777 40

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

HLA class I expression was studied in 43 specimens of normal renal tissue, 48 primary renal cell carcinomas (RCCs), and 12 metastases by immunofluorescence, using two different monoclonal antibodies (MoAbs; IOT2c, W6/32). Homogenous staining of all normal renal tissues was observed, as expected. From the panel of 48 renal tumors, 40 had a strong expression of HLA class I antigens when tested with both MoAbs, 7 tumors had only weak expression of HLA class I and were regarded as 'HLA class I negative', and 1 tumor showed homogenous staining when tested with one MoAb (IOT2c) but was negative when the other was used (W6/32). This was the only case in which different results with the two MoAbs were found. Reduced expression of HLA class I antigens was observed in 5/12 metastases, and in 1 metastasis no expression of HLA class I could be seen. The staining chartacteristics of 10 metastases in comparison with the respective primary tumors were as follows: same HLA class I score 7/10; loss of HLA class I 3/10; gain of HLA class I 0/10. In RCC, a complete loss of HLA class I expression is a rare phenomena, which was observed in 0/48 primary tumors and in 1/12 metastases. Reduced expression of HLA class I antigens occurs in about 15% of primary tumors but is more frequent (50%) in metastases; however, if this is relevant for cytotoxicity by T lymphocytes is unknown.
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PMID:Immunohistochemical studies on the expression of HLA class I antigens in renal cell carcinoma: comparison of primary and metastatic tumor tissue. 813 58


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