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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently described marked differences in cell migration rates and organization of actin in human melanoma cell lines isolated from various stages of tumor progression. Metastatic lines derived from lymph node metastases organized actin into stress fiber arrays and had high mean migration rates in vitro when compared to lines from other stages. Melanoma cells also reveal marked differences in localization of alpha-actinin and beta 1 integrins at stress fiber termination sites (focal contacts). Disruption of this organization is induced by antibodies against beta 1 integrins, alpha-actinin, recently postulated as having a role in linkage of actin to beta 1 integrins, is differentially expressed in melanoma cells by Northern blot analysis and a relatively high alpha-actinin to actin ratio is associated with stress fiber formation and increased cell migration. Furthermore, actin-binding protein, which cross-links actin filaments, is also significantly increased in lines exhibiting high migration rates. Control of migration and actin organization may be mediated by extracellular matrices and/or modulation of actin-associated proteins including alpha-actinin and actin binding protein. These findings provide evidence that an interaction of transmembrane adhesion molecules and elements of the cytoskeleton in melanoma cells may be responsible for differences in migration rates and capacity for metastasis.
J Dermatol 1992 Nov
PMID:Actin organization and cell migration of melanoma cells relate to differential expression of integrins and actin-associated proteins. 129 73

The use of non-radioactive in situ hybridization (ISH) with chromosome-specific repetitive DNA probes to study genomic changes, aneuploidy, and heterogeneity during melanocytic tumor progression, relies on its applicability to non-mitotic interphase nuclei, present in cell suspensions and tissue sections. Therefore, we studied the feasibility of detecting numerical aberrations with respect to the (peri-) centromere regions of chromosomes 1 and 7 in intact nuclei of two human melanoma cell lines with different metastatic behavior in nude mice. In addition, we used paraffin sections from xenograft lesions, obtained by inoculation of these cell lines in nude mice (subcutaneous tumors and spontaneous lung metastases). Paraffin sections from the original primary cutaneous melanoma (with a subepidermal and a dermal part) and two loco-regional metastases were also studied, one of which was the source for the cell lines. These cells and tissues represent examples of materials used in different approaches to the study of melanocytic tumor progression. Regarding the targeted sequences, ISH analysis showed that both cell lines were heterogeneous and aneuploid. The results correlated well with those obtained by ISH on metaphase spreads. Differences between the lines, which could not be detected by flow-cytometric or conventional karyotyping analysis, included data suggestive of a polyploid subpopulation and an extra copy of chromosome 7 in the metastasizing cell line. The polyploid population could be detected also in the paraffin sections of the corresponding subcutaneous xenografts and lung metastases in the mice. Both areas in the patients' primary melanoma could be evaluated separately and showed similar supernumerary aberrations of the chromosome-specific targets. These abnormalities matched those found in both metastases. Our results demonstrate that ISH can be used to visualize genomic abnormalities at the single-cell level in melanocytic nuclei in their natural context, which makes it a promising tool in the histopathology of melanocytic lesions and in the study of melanocytic tumor progression.
J Invest Dermatol 1992 Apr
PMID:In situ detection of supernumerary aberrations of chromosome-specific repetitive DNA targets in interphase nuclei in human melanoma cell lines and tissue sections. 154 28

Different results have been reported on the expression of epidermal growth factor receptor (EGFR) in human melanocytic lesions, which may be due to different methodologic approaches. Therefore, we compared EGFR expression in six human melanoma cell lines by utilizing the monoclonal antibodies 2E9, 425, and 225, applying four immunocytochemical staining procedures. The results were compared with those obtained by a multiple point ligand binding assay. In addition, Northern blot analysis was performed. A three-step immunoperoxidase method using the monoclonal antibody 2E9 proved most sensitive. Staining intensities, estimated semiquantitatively, correlated well with the quantitative data obtained by the ligand-binding assay. Expression on the mRNA level was also in agreement with these results. Immunohistochemical staining of a large series of human cutaneous melanocytic lesions using the method selected showed differential EGFR expression in various stages of melanocytic tumor progression: 19% of common nevocellular nevi; 61% of dysplastic nevi, 89% of primary cutaneous melanomas, and 91% of melanoma metastases showed staining of the melanocytic cells. Intralesional heterogeneity of EGFR expression was present. Although the mean percentage of positive melanocytic cells in positive lesions did not increase with progression, mean staining intensity was stronger in malignant lesions compared to benign lesions. Ligand binding assays showed that EGFR expression in the highly metastasizing cell lines MV3 and BLM was at least 40 times higher than in the cell lines IF6, 530, M14, and Mel57, which do not or only sporadically metastasize after subcutaneous inoculation in nude mice. Although the differences between the various stages of progression are not absolute, we provide further evidence that EGFR expression increases in human melanocytic tumor progression.
J Invest Dermatol 1992 Aug
PMID:Increasing epidermal growth factor receptor expression in human melanocytic tumor progression. 162 28

Advanced steps of tumor progression are generally characterized by an increased growth fraction within the neoplastic cell population. The presence of a relevant growth fraction is also related to widely accepted prognostic parameters in some human malignancies. Our aims were to evaluate the presence of a growth fraction with Ki67 monoclonal antibody (MoAb), and to correlate it with tumor progression and HLA-DR antigen expression in 88 melanocytic lesions. The lesions were 19 acquired melanocytic nevi, 58 primary melanomas [divided into 26 superficial spreading melanomas (SSM), 24 superficial spreading melanomas with nodular areas (SS + NM), and five nodular melanomas (NM)], and 11 metastases from malignant melanomas. Ki67 MoAb stained 16%, 19%, 71%, 100%, and 82% of nevi, SSM, SS + NM, NM, and metastases, respectively. Among primary melanomas, Ki67 MoAb stained 12%, 28%, 50%, and 70% of tumors less than 0.75, 0.75-1.49, 1.5-2.9, and greater than or equal to 3 mm thick, respectively. A concordant reactivity pattern for Ki67 and HLA-DR antigens was found in 72% of lesions (p less than 0.0001). We have shown that a representative growth fraction (ie, Ki67 reactivity) is present in melanocytic lesions only in advanced steps of tumor progression and correlates with HLA-DR antigen expression. Despite the different biologic values of Ki67 and HLA-DR antigens, we suggest the joint evaluation of both antigens as a useful marker of aggressive behavior in melanoma.
J Invest Dermatol 1990 Sep
PMID:Ki67 antigen expression correlates with tumor progression and HLA-DR antigen expression in melanocytic lesions. 169 3

Angiosarcoma of the face and scalp developed in 12 patients. The patients were five women and seven men with an average age of 71 years. Initial features were solitary or multiple violaceous vascular nodules or plaques. The clinical course was complicated by ulceration, secondary infection, bleeding, anemia, infiltration into the underlying bones, tumor cachexia, and death. Metastases were not observed. Histologically, seemingly benign hemangiomatous capillary-like structures were found in some areas of the tumors, with richly cellular, solid sarcomatous proliferations in other areas. Early and extensive surgical excision is the therapy of choice, but generally it does not alter the relentless course of the disease. Neither palliative radiation therapy nor polychemotherapy is capable of interfering with tumor progression.
Int J Dermatol 1991 Dec
PMID:Angiosarcoma of the face and scalp. 181 27

Some early changes associated with atypical nevi, presumed to be progressing toward malignancy, include chromosomal abnormalities and altered production of growth factors, and/or growth factor receptors. Though normal epidermal melanocytes require a number of exogenous growth factors, nevi require fewer growth factors, and most metastatic melanomas are frequently capable of growing without an exogenous supply of growth factors. This is apparently caused by endogenous production of essential growth factors. Our laboratory focuses on melanoma growth stimulatory activity (MGSA), one of the endogenously produced growth factors, and the role it plays in tumor progression. MGSA is a member of the beta-thromboglobulin super family. These genes code for cytokines, which modulate the inflammatory response. The MGSA protein is highly chemotactic for neutrophils and competes with 125I-interleukin-8 for binding sites on neutrophil receptors. When normal immortalized mouse melanocytes are manipulated so that they overexpress the MGSA gene, the melanocytes form large colonies in soft agar and melanoma tumors in nude mice. These data suggest that the MGSA protein can potentially play a role in melanoma tumor progression.
Semin Dermatol 1991 Sep
PMID:The pathogenic role of growth factors in melanoma. 193 74

The expression of the integrin receptors VLA-1, -2, -3, and -6 was studied in normal cultured melanocytes and in five melanoma cell lines. Normal melanocytes synthesized VLA-3, but did not reveal detectable levels of VLA-1, -2, and -6. All melanoma cell lines, however, expressed VLA-2, -3, and -6. VLA-1 was synthesized by two of five melanoma lines. In parallel, we had analyzed the expression of four previously characterized melanoma cell surface antigens. One of them (antigen A.1.43), which is associated with tumor progression of human melanoma, revealed a striking similarity to VLA-2. In sequential immunoprecipitation experiments, we show that A.1.43 is identical with the integrin VLA-2, a cell surface receptor for collagen, laminin, and fibronectin.
J Invest Dermatol 1991 Feb
PMID:Identification of a melanoma progression antigen as integrin VLA-2. 199 90

Monolayer cultures of the human melanoma cell lines StML-12, StML-11, StML-14 (third, respectively, twenty-fifth subculture), and SKMel-28 derived from specimens representing different stages of tumor progression were treated with 10-10,000 U/ml rTNF-alpha applied for 72 h. The effects of rTNF-alpha on cell proliferation, DNA synthesis, cell viability, cloning efficiency, cell division, cell morphology, and the immunophenotype were studied in triplicate experiments. The cell line StML-14(3) revealed a significantly dose-dependent reduction of growth due to both cytostatic and cytotoxic activities of rTNF-alpha as well as a decrease of CE. Increased numbers of cells in prophase were observed 24 h after addition of r-TNF-alpha. In addition, dislocation of chromosomes in the metaphase, formation of micronuclei, and dose-dependent increases of cells exhibiting micronuclei and the DNA amount per cell were detected at the end of treatment. On the other hand, only a slight sensitivity to the anti-proliferative effect of rTNF-alpha was observed with StML-14(25) and SKMel-28, whereas StML-12 and StML-11 were significantly resistant. The last four cell lines were serially subcultivated and presented common phenotypic patterns with more malignant characteristics than the cell line StML-14(3) before treatment. Overall, rTNF-alpha enhanced the malignant immunophenotype of the cell lines tested. It increased the expression of the "late" melanoma progression markers A.10.33 and A.1.43, and Ki67, and it decreased the expression of the "early" progression marker K.1.2. The expression of HLA-I, HLA-DR, and ICAM-1 was also enhanced after rTNF-alpha treatment, whereas in contrast to other cytokines, rTNF-alpha did not induce the de novo expression of HLA-DR in HLA-DR-negative melanoma cell lines. These findings indicate that rTNF-alpha induces cytostasis and decreases cell viability of certain rTNF-alpha-sensitive melanoma cells. These effects may result in selection of rTNF-alpha-non-sensitive human melanoma cell populations with higher proliferation rates and a more aggressive immunophenotype in vitro.
J Invest Dermatol 1990 Dec
PMID:Cytostatic and cytotoxic effects of recombinant tumor necrosis factor-alpha on sensitive human melanoma cells in vitro may result in selection of cells with enhanced markers of malignancy. 225 39

Based on melanoma pathogenesis, phenotypic dynamics in pigment cell tumor progression detected with 11 MoAb have been defined. Anti-melanosomal A4F11 antibody reacts with every type of pigment cell tumor tested except for a few specimens. TNKH1 and anti-K.1.2 antibodies recognize nevocytic benign to premalignant tumors. HLA-DR, A.1.43, and A.10.33 antigens are expressed in advanced melanomas. Staining with anti-ganglioside GM3 and GD3 antibodies, M2590 and 4.2, respectively, reveals that most pigment cell tumors express gangliosides GM3 and GD3. But A2B5 antibody, which detects some polysialogangliosides such as GQ1C, reacts with highly progressed melanoma cells. Anti-ras p21 antibodies, RASK-3 and RASK-4, react with malignant melanomas and their premalignant lesions. These findings suggest the following: A4F11 is a universal marker of pigment cell tumors. TNKH1 and anti-K.1.2 antibodies might not be markers of melanocytic tumors but of nevocytic benign to premalignant tumors. Melanoma cells express gangliosides GM3 and GD3 as common pigment cell antigens and synthesize aberrant polysialogangliosides. Anti-ganglioside MoAb, including A2B5, are possible markers of the level of malignancy in melanoma cells like anti-A.1.43 and anti-A.10.33 antibodies. Enhanced ras p21 expression already appears on premalignant pigment cells.
J Invest Dermatol 1990 Feb
PMID:Antigen dynamics in melanocytic and nevocytic melanoma oncogenesis: anti-ganglioside and anti-ras p21 antibodies as markers of tumor progression. 229 92

Two hypotheses have been presented. The first states that melanomas commonly evolve from normal melanocytes by a tumor progression pathway from a banal nevus to a nevus with dysplasia, to a micro-invasive, and then to a fully evolved, tumorigenic, primary melanoma which has competence for metastasis. It is important to note that not all melanomas follow this complete pathway. As Foulds noted long ago, tumors may bypass any of the stages of tumor progression. Thus, many melanomas do not, apparently, arise in nevi, and melanomas may evolve "fully formed" as pure tumorigenic nodules. However, from the biological point of view, study of the benign potential precursors (nevi and, especially, dysplastic nevi as well as microinvasive melanomas) may well reveal mechanisms of progression that are applicable to all melanomas, and perhaps to other solid tumors as well. From a clinical viewpoint, follow-up and education of patients at increased risk for melanoma, and early diagnosis of melanomas in their curable, microinvasive stages may result in a reduction of mortality from the disease, even without influencing its overall incidence. The melanomas that occur on plantar and palmar (acral) skin appear to progress through a microinvasive stage similar to that of other cutaneous melanomas. However, the significance of precursor and marker lesions (if any exist) in acral melanoma remains to be elucidated by clinicopathologic and epidemiologic studies. The possibility of etiologic agents other than UV light, such as chemical carcinogens and/or viruses, should be investigated in these cases. The second hypothesis presented here, that UV light is etiologic for the common cutaneous melanoma of white populations, has support from clinical, epidemiologic, and biologic observations. From a biologic viewpoint, ultraviolet light has all of the properties that might enable it to act as a complete carcinogen, and to enhance tumor progression in melanocytic "potential-precursor" lesions. Clinically, it seems appropriate to encourage patients (and members of the general population, as well) to adopt sensible attitudes to sun exposure. By such means, it is possible that some melanomas might be prevented, or that the rate and incidence of progression to more-advanced stages might be inhibited.
J Invest Dermatol 1989 May
PMID:Human melanocytic neoplasms and their etiologic relationship with sunlight. 265 3


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