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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tenascin is a large glycoprotein of the extracellular matrix. It shows a site-restricted expression during embryogenesis and can be found in adult tissues during wound healing and tumorigenesis. Because of the potential involvement of tenascin in adhesion and invasion during metastasis, the study of the interactions of tumor cells with tenascin is of considerable interest. Using five anti-melanoma monoclonal antibodies to four different epitopes of human tenascin, we found that most melanoma cells secrete tenascin in vitro constitutively. Transforming growth factor beta 1 in the medium increased secretion in tenascin-producing cells. Tenascin was present in sera of melanoma patients, with significantly elevated levels in patients with advanced melanomas as compared to patients with low tumor burden or to normal donors. Normal and malignant melanocytes did not attach to tenascin as substrate within 1 to 2 h and tenascin could also inhibit fibronectin-dependent adhesion. These results indicate that tenascin may play a critical role in cell-substrate interactions of melanoma cells.
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PMID:Characterization of tenascin secreted by human melanoma cells. 171 15

A common feature of human melanoma is infiltration by monocytes at early stages of tumorigenesis. This infiltration may be highly significant since macrophages have the capacity to alter the behavior of tumor cells. The authors previously demonstrated that the predominant monocyte chemoattractant produced by tumor cells in vitro was monocyte chemotactic protein-1 (MCP-1). The authors identify the expression of MCP-1 in pathologic specimens of both primary and metastatic human melanoma but not in normal skin. The finding that MCP-1 is produced by malignant melanoma suggests that specific genes are expressed in tumor cells that can induce the recruitment of monocytes in vivo.
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PMID:Expression of monocyte chemotactic protein-1 in human melanoma in vivo. 173 32

Assessment of the function of putative dominantly-acting oncogenes or recessive tumor-suppressor genes in human tumor development and progression must ultimately involve xenografting experiments using immune deficient animals such as nude mice. Most human tumor xenograft experiments have employed conventional subcutaneous injection procedures. However, despite the simplicity of this procedure, it poses some serious potential drawbacks as most types of human tumor will not readily grow or metastasize from a subcutaneous ('ectopic') site of injection. In contrast, 'orthotopic' injection procedures will often enhance the tumorigenic and/or metastatic ability of tumor cell populations. An example of this is summarized in the context of human malignant melanoma where the effects of subcutaneous versus subdermal injection are compared. Despite the seeming subtle and minor change in injection site, superior growth of human melanomas can be obtained by the latter, orthotopic-like, route of injection. It therefore follows that induction of tumorigenic or metastatic properties in a given human cell population by gene transfection may not be detected if the transfected cells are assayed in vivo only by subcutaneous injection procedures. An example of this is provided by experiments involving transfection of normal or mutated ras genes into a low-grade, well-differentiated human bladder carcinoma cell line, called RT-4. Thus overexpression of normal or mutated (valine 12) c-H-ras resulted in acquisition of a clinical-like invasive phenotype. However, this was clearly seen only if the cells were injected into the bladders (i.e. 'intravesically') of nude mice. In contrast, conventional subcutaneous injection of the high ras expressing transfected RT-4 cell lines did not reveal acquisition of invasive properties: all cell lines grew locally as well-encapsulated tumor masses. It is argued that similar orthotopic injection procedures should be employed when assessing the suppressive effects of various wild-type tumor-suppressor genes on human tumor growth in vivo. Utilization of subcutaneous injection procedures may grossly exaggerate the growth suppressive effects of such genes. This could explain the paradox of why, on the one hand, alterations involving many different genes (including different suppressor genes) appear to be involved in human carcinoma tumorigenesis while on the other hand, complete suppression of tumorigenicity can be caused by transfer of a single wild-type suppressor gene. Such complete suppressions might be observed only after ectopic (usually subcutaneous) injection procedures.
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PMID:Importance of orthotopic transplantation procedures in assessing the effects of transfected genes on human tumor growth and metastasis. 176 65

Growth factors and proto-oncogenes play an important role in the regulation of embryonic growth and differentiation as well as in tumorigenesis. Insulin and insulin-like growth factor I (IGF I) are secreted by embryonic tissues during the prepancreatic stage of mouse development. Measureable amounts of these factors were found in 8- to 12-day-old embryos. Embryonic cells derived from 8- to 10-day-old embryos secrete insulin and IGF I in serum-free medium. Relatively high levels of c-myc, c-fos and c-H-ras oncoproteins were also detected in 8- to 12-day-old embryos. Insulin and IGF I, when added to the culture of embryonic cells, stimulate their proliferation. Similar results were obtained in some animal or human tumors. Murine myeloid leukemias and melanoma B 16 secrete a substance immunologically cross reactive with insulin (SICRI) both in vivo and in serum-free media. In culture, the DNA synthesis rate per leukemic or melanoma cell is proportional to cell density and is reduced by antiinsulin serum in case of leukemic cells. Human hemangiosarcoma secrete IGF I, which also plays a role as an autocrine factor. Purified IGF I efficiently induce c-myc and c-fos mRNA, which is among the earliest events following growth factor stimulation, leading to mitosis. These results lead us to the conclusion that IGF I and insulin together with oncoproteins stimulate the growth of embryonic and tumor cells, which is indirect evidence for a paracrine (or autocrine) type of action.
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PMID:Growth factors and proto-oncogenes in early mouse embryogenesis and tumorigenesis. 181 4

Reduced expression and/or somatic allelic deletion of nm23 is associated with high metastatic potential in several types of rodent tumors and human breast and colorectal carcinomas. Transfection of murine nm23-1 cDNA into highly metastatic murine K-1735 TK melanoma cells results in a reduced incidence of primary tumor formation, significant reduction in tumor metastatic potential, and altered responsiveness to the cytokine, transforming growth factor beta. Here we discuss emerging concepts concerning nm23, such as its varied pattern of alteration/expression in tumor metastasis, its effect on tumorigenesis, and its possible biochemical functions.
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PMID:Tumor metastasis and nm23: current concepts. 191 Oct 39

We have investigated the ability of metastatic cells to produce the macrophage cytokine, TNF-alpha/cachectin, as these cells have macrophage-like properties such as infiltration and migration. We looked for TNF-alpha/cachectin in three tumor cell lines derived from human malignant melanomas and six co-cultivated malignant melanomas derived, in vitro, from these three cell lines plus angioma fibroblasts. Immunohistochemistry with an anti-TNF-alpha/cachectin monoclonal antibody showed that TNF-alpha/cachectin was produced by two of the three parent melanoma cell lines. All the tumor cells in both the co-cultivated malignant melanomas and their in vitro tumorous nodules produced TNF-alpha/cachectin, even those derived from the melanoma cell line, which originally did not. The results clearly show that TNF-alpha/cachectin can be produced by non-hematopoietic tumor cells. A co-cultivated tumor model prepared from other types of human tumor cell lines promises to provide a useful tool for exploring the relationship between TNF-alpha/cachectin and oncogenesis.
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PMID:Immunolocation of TNF-alpha/cachectin in human melanoma cells: studies on co-cultivated malignant melanoma. 199 83

Genetic and molecular analyses of Drosophila have shown that tumorigenesis may arise from inactivation of single genes controlling cell growth and differentiation. Recessive mutations in a series of genes interrupt the differentiation of primordial cells and result in overgrowth, producing either hyperplasia or neoplasia. In mutant animals tumours form in either the optic centres of the larval brain, the imaginal discs or the haemopoietic organs. In Drosophila 17 genetic loci giving rise to neoplasia and six loci producing hyperplasia have been identified. The lethal(2)giant larvae gene constitutes the prototype of these genes. Its molecular cloning and analysis have demonstrated that the tumor phenotype results from a lack of gene function. Furthermore, tumour prevention was achieved by introducing a normal copy of l(2)gl into the genome of l(2)gl- deficient animals, showing that the l(2)gl gene behaves as a tumour suppressor or anti-oncogene. Melanomas of genetic origin develop in interspecies hybrids of the fish Xiphophorus. The melanoma appears when a sex linked chromosomal gene (Tu) is present among the progeny animals lacking an autosomal locus Differentiation, which acts as a tumour suppressor gene. A sequence homologous to the erb-B gene can be associated to the sex chromosomal Tu locus. This gene encodes a receptor tyrosine kinase related to the EGF-receptor, and its activation and overexpression are thought to play a critical part in melanoma formation.
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PMID:The fruit fly Drosophila and the fish Xiphophorus as model systems for cancer studies. 210 23

Sunlight, particularly its UVB component, is thought to be the most important environmental factor for oncogenesis of melanoma. Its intensity, at the ground level, is a positive function of altitude and a negative function of latitude. Sun exposure and susceptibility in childhood seem to be major risk factors at least in Anglo-saxon countries. UV radiations are able to act as complete carcinogen. Eumelanin/pheomelanin ratio also appears as an important risk factor. Ionizing radiations, heat and traumas have been seldom related to melanoma carcinogenesis. Several chemicals, among them drugs and toxic drugs, add to the list of possible causative agents. Loss of alleles encoding for suppressor factors, caused by UV radiation, might play a significant role in carcinogenesis. A model is proposed, for "mediterranean" vs "caledonian" melanoma, in which the phenotypic sequence melanocytic nevus----melanoma would exhibit peculiar characteristics.
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PMID:[Etiopathogenesis of malignant melanoma of the skin. III. Disease factors inherent in the environment. Pathogenetic hypothesis]. 219 29

Experience has shown that markers created in research laboratories can be adapted to everyday surgical pathology practice for malignant melanomas. These studies are feasible and readily conducted on frozen tissue as is routinely done in typing of lymphoma. The demonstration of heterogeneity using this monoclonal antibody panel, and other antibodies yet to come, may be important for prognostication. Tumor cell heterogeneity of surface antigens reflects disruption of the tumor cell's patterned gene expression. This should be regarded as an indication of different clones of cells (subsets) with a tumor, whether primary or secondary. It is entirely possible that autologous immune cells can kill or at least restrict the growth of subsets of melanoma cells having certain surface antigenic phenotypes while they are incompetent to handle other subsets. This would enable a particular phenotype within a primary melanoma to survive and escape the immunologic regression known to occur in 3 to 6 percent of these tumors. Such patients may present years later with metastases in the brain, liver, gastrointestinal (GI) tract, or lymph nodes. There are also implications in chemotherapy and chemoimmunotherapy for melanoma in this regard. It could be theorized that these agents may dispose of or restrict the growth of some phenotypes, leaving others in a resistant state. Perhaps the MDR gene is activated. Alternatively a tumor suppressor gene(s) could be absent or inactivated, as in neuroblastoma and carcinoma of the breast and lung. Markers present at the cell membrane surfaces and in the membranes themselves constitute an important field for study in the understanding of tumorigenesis. Many of these markers are present in embryos as early as the 4-to-8-cell stage and in blastocysts. Embryonic antigens in the intercell mass of blastocysts are stage-specific embryonic antigens. They are signals for organ development and the differentiation of cells. At various stages of this development, these markers disappear, especially upon differentiation into tissue types and specific organs. These cell signals are therefore organogenesis markers. Detecting a given antigen is not simple because it may be present but not immunohistochemically detectable because glycosylation, acetylation, phosphorylation, or sulfation have not taken place, or have resulted in a structural conformation not recognized by monoclonal antibodies.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Immunohistochemical phenotyping of malignant melanoma. A procedure whose time has come in pathology practice. 220 65

Cytogenetic analysis performed on 11 human malignant melanoma cell lines that were passaged through nude mice revealed both numerical and structural types of chromosomal defects. Banding analysis showed structural anomalies in chromosomes 1, 3, 5, 6, 7, 9, 10, 11, 14 and 15. Of these, the most frequently involved chromosomes were 6, 7, and 9. Chromosomes 3 and 11 were next with chromosomes 5 and 10, the least involved. Our results were very similar to results published in the literature on melanoma cytogenetics except that we found additional chromosomal alterations. Most frequently involved structural anomalies of the short arm of chromosome 9 and the long arm of chromosome 6 have been interpreted as primary and secondary defects, respectively, in melanocyte oncogenesis.
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PMID:Consistent karyotypic abnormalities in human malignant melanomas. 238 82


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