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

The effect of retinoic acid pretreatment on metastatic B16 melanoma cell adhesion in serum-free medium to tissue culture plastic precoated with fibronectin, laminin/nidogen, type I and type IV collagen was examined. Both control cells grown to subconfluence and cells treated with 10(-6) M-retinoic acid adhered and spread rapidly on fibronectin (greater than 75% following 1 h of incubation) but adhered poorly to type I collagen (less than 15%). Control cells adhered to laminin/nidogen (greater than 35%), type IV collagen (greater than 58%) and type IV collagen plus laminin/nidogen (greater than 80%), while retinoic acid-treated cells showed a reduced ability to attach and spread on these substrata, the number of adherent cells being reduced by 61% on laminin/nidogen, by 19% on type IV collagen, and by 41% on type IV collagen plus laminin/nidogen following 1 h of incubation. The minimum concentration of retinoic acid required to yield an effective reduction in adhesion was 10(-7) M for type IV collagen and 10(-10) M for laminin/nidogen. Melanoma cells harvested at low density showed a reduced adhesion to laminin/nidogen and type IV collagen compared to that of subconfluent control cultures, but also showed a reduced adhesion to fibronectin. The effect of retinoic acid on cell adhesion was not, however, due to reduced cell density, as the cells were seeded so that control and retinoic acid-treated cultures were of a similar density when harvested.
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PMID:Modulation of melanoma cell adhesion to basement membrane components by retinoic acid. 261 55

Studies with four different transplantable murine tumors demonstrated that surgical instruments contaminated by contact with a tumor mass could produce tumors in a surgical wound. Eighty-seven per cent of mice with wounds made by invisibly contaminated scissors developed tumors. Irrigation with water did not prevent tumor growth. Before spilled tumor cells can invade and grow into a recurrence in the wound site, they must first attach to underlying extracellular matrix. We have devised a simple in vitro assay to identify inhibitors of tumor-cell attachment to develop therapeutic compounds that can prevent tumor-cell reimplantation. Various test compounds, including proteases (trypsin and Dispase), known modulators of matrix metabolism (proline analogues, cycloheximide, heparin, cortisone, cortexolone, and heparin-steroid combinations), large molecular weight polymers (agarose, dextran, polyethylene oxide), and synthetic fibronectin peptides were tested for their ability to inhibit mouse melanoma (B16-F10) cell attachment to gelatinized dishes. Most of these compounds had little or no effect on tumor-cell adhesion when cells were plated in serum-containing medium. However we identified three compounds that inhibited tumor-cell attachment in a reversible fashion: (1) a specific inhibitor of collagen deposition (L-azetidine-2-carboxylic acid); (2) a bacterial neutral protease (Dispase); and (3) synthetic fibronectin peptides that contained the arginine-glycine-asparate (RGD) sequence that is responsible for cell binding. Dispase and the RGD-containing peptides also inhibited cell implantation and prevented tumor formation in a surgical wound. We propose that inhibitors of attachment might be used either alone or with other biologic modifiers to prohibit implantation of free tumor cells at the time of surgery and thus, to prevent local tumor recurrence.
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PMID:Inhibition of tumor-cell attachment to extracellular matrix as a method for preventing tumor recurrence in a surgical wound. 268 68

A new technique was developed to coat Nuclepore filters with basement membrane matrix components. Using the EHS tumour as a source, a proteoglycan and laminin-containing fraction was extracted with guanidine and collagen type IV was solubilized in a second fraction by limited digestion with pepsin. When the two fractions are combined and guanidine removed by dialysis, a gel is rapidly formed. A flat-bed dialysis apparatus was devised, allowing gels to form on filters that are soaked in the mixture, thus coating them with components of the basement membrane. Such filters were used for selection of B16 melanoma cells penetrating the gels. 10 clones were isolated after three selection passages, and assayed for spontaneous metastasis in C57Bl/6 mice after intracutaneous injection. The metastasis rates were strongly increased to the lungs and to inguinal and axillary lymph nodes. Less accessible sites such as mediastinal and maxillary lymph nodes were reached only by selected cells. There was no particular preference for the haematogenous or lymphatic routes, indicating that the ability to traverse the basement membrane leads to a general increase of metastasis. The described method provides a valuable tool for isolating those subpopulations able to traverse basement membranes and to assess this capacity in new tumour samples.
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PMID:Selection of highly malignant tumour cells using reconstituted basement membrane matrix. 270 99

An immunohistochemical and ultrastructural study of human melanoma colonies grown in soft agar for up to 50 days was performed. Three morphological variants of developing tumor colonies are reported: 1) large light colonies, 2) small dark colonies, and 3) smooth-edged colonies. The large light colony variant is the most frequently observed in the soft agar assay (approximately 70%), followed by the dark colony variant (approximately 27%), and the smooth-edged colony variant (approximately 3%). Major morphological characteristics are associated with each variant, as shown with light microscopy (LM) and transmission electron microscopy (TEM). Both LM and TEM analyses demonstrated that the large light colony variant was hypomelanotic and contained a microfibrillar extracellular matrix (ECM). The small dark colony variant was found to be hypermelanotic and contained a less demonstrable ECM. The smooth-edged variant has an encapsulated periphery, no demonstrable ECM, and tightly packed cells with desmosome-like junctions. In order to characterize further the ECM in the most commonly observed variant, the large light colony, specific antibodies to fibronectin (FN) and collagen types IV and V (COLs IV and V) were applied and observed with immunofluorescence microscopy and immunoperoxidase. In paraffin sections of melanoma colonies, FN was observed associated with both the cell surface and the ECM. However, no specific staining was seen for COLs IV and V. In addition, ruthenium red was used to preserve and selectively bind to glycosaminoglycans (GAGs) and proteoglycans (PGs). TEM studies reveal GAG-like granules stained with ruthenium red in the fibrillar ECM and a dotted, punctate staining of the cell surface. Understanding the biological and architectural composition of developing melanoma tumor colonies in soft agar could contribute to the development of more efficient chemotherapeutic strategies.
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PMID:Immunohistochemical and ultrastructural study of human melanoma colonies grown in soft agar. 275 Jun 77

To the best of our knowledge anchoring fibrils in tumours have been reported to occur only in cutaneous cylindromas and squamous cell carcinomas of oral mucosa and larynx. In this paper we describe a difficult-to-diagnose malignant spindle cell tumour where the striking feature was the presence of large numbers of anchoring plaques and anchoring fibrils in the tumour matrix. On the basis of light microscopic and immunohistochemical studies several diagnoses were preferred, such as malignant fibrous histiocytoma, neurofibrosarcoma, malignant schwannoma, desmoplastic melanoma and spindle cell squamous carcinoma (more fully referred to as 'spindle cell variant of squamous cell carcinoma'). The presence of anchoring fibrils in this tumour strongly supports the diagnosis of spindle cell squamous carcinoma. Our knowledge about the occurrence of anchoring fibrils in tumours is scant, perhaps because they are likely to be missed unless they are present in large numbers, or perhaps because they are mistaken for native collagen fibrils. It seems to us that a systematic search for anchoring fibrils in tumours is warranted, for knowledge about their occurrence or absence in various types of tumours may add yet another diagnostic marker in the armamentarium of the diagnostic electron microscopist and it may also assist in resolving the histogenesis of some controversial neoplasms.
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PMID:Anchoring fibrils in a spindle cell squamous carcinoma. 275 58

Tumor cell metastasis involves a complex series of interdependent events, including repeated invasion of basement membranes. Studies from several laboratories have implicated tumor cell adhesion and migration in response to laminin as a major contributing factor in tumor cell invasion. The current studies address the direct role of type IV collagen in promoting tumor cell adhesion, spreading, and migration. The observations of type IV collagen-mediated cellular behavior are contrasted with cellular behavior on type I collagen. The highly metastatic K1735 M4 melanoma cell line adhered, spread, and migrated in response to type IV collagen in a concentration-dependent manner. Functional assays using well-defined proteolytic fragments of type IV collagen demonstrated that melanoma cells interact with multiple domains of this protein. Highly metastatic melanoma cells adhered, spread, and exhibited motile behavior in response to 0.2 to 200 nM concentrations of a purified pepsin-generated, triple helix-rich domain of type IV collagen. In contrast, cells adhered and spread but were essentially nonmotile in response to a purified major noncollagenous domain of the protein. In addition, de novo protein synthesis was required for cell adhesion to the major noncollagenous domain, whereas adhesion to the helical domain was less dependent upon de novo protein synthesis. Arg-Gly-Asp (RGD)-related peptides were used to study the adhesion and spreading of melanoma cells on type IV collagen. The results demonstrated that a serine containing RGD-related peptide (GRGDSP) has virtually no effect on melanoma cell adhesion on type IV collagen-coated substrata, whereas this peptide inhibited melanoma cell adhesion to fibronectin-coated substrata in a concentration-dependent manner. In contrast, when threonine was substituted for serine (GRGDTP), cell adhesion to type IV collagen was significantly (45%) inhibited. The threonine-containing peptide virtually eliminated cell adhesion on substrata coated with type I collagen. These data demonstrate that adhesion, spreading, and migration of melanoma cells on type IV collagen have a complex molecular basis which is partially dependent on RGD-related sequences.
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PMID:Type IV collagen-mediated melanoma cell adhesion and migration: involvement of multiple, distinct domains of the collagen molecule. 275 12

Two patients with epibulbar juxtalimbal primary conjunctival melanomas experienced local intralymphatic metastases to the inferior cul-de-sac, and a hematogenous metastasis to the conjunctiva developed in five other patients with cutaneous melanomas. Whether reflective of a local or distant metastasis, all of the lesions histopathologically were located in the substantia propria, and were separated from the overlying epithelium by a thin mantle of collagen. There was no evidence of atypical intraepithelial melanocytic proliferation, as would be expected in association with a primary conjunctival melanoma. Two of the cutaneous metastases exhibited a binodular or multinodular appearance that correlated histopathologically with variably confluent micronodules suggestive of the origin of the clinical lesion from a shower of tumor cell emboli. Patients with local intralymphatic spread from a primary conjunctival melanoma may experience additional lesions in the conjunctival sac or eyelid skin and are at risk for regional or distant metastases. They should be examined closely several times a year. The patients with the distant metastases all had their previously diagnosed primary cutaneous tumors on the truncal skin (a similar tendency emerges from a review of previous ocular cases), typically had myriad other cutaneous lesions, and two of them had a neoplastic iridocyclitis and vitreitis. These patients tended to die of the disseminated tumors within 1 year after conjunctival metastases developed.
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PMID:Metastatic melanoma within and to the conjunctiva. 277 66

Patterns of basement membrane deposition were investigated in benign and malignant naevo-melanocytic lesions using antibodies to type IV collagen and laminin. Paraffin sections required pretreatment with 6 M guanidine-HCl in addition to pepsin pretreatment. Basement membrane deposition was found around clusters as well as individual naevo-melanocytic cells in contact with dermal stroma. However, between keratinocytes and intra-epidermally located naevo-melanocytic cells, basement membrane immunostaining could not be detected. Tumour cell-stromal interaction is apparently a prerequisite for basement membrane deposition in naevo-melanocytic lesions. Basement membrane discontinuities, in the absence of inflammatory infiltrate, appeared, in doubtful cases, to be evidence in favour of malignant melanoma. The general pattern of basement membrane deposition in benign and malignant lesions was found to be similar and therefore of no help in differential diagnosis. Identification of hyaline bodies, which show immunoreactivity with antibodies to basement membrane components, may be helpful in distinguishing between Spitz naevi and malignant melanomas. Detection of vascular invasion, a prognostic indicator in malignant melanoma, is facilitated by basement membrane immunostaining.
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PMID:Basement membrane deposition in benign and malignant naevo-melanocytic lesions: an immunohistochemical study with antibodies to type IV collagen and laminin. 277 16

Using both human and murine cell lines, we show that malignant cells are able to invade through basement membrane and also secrete elevated amounts of collagenase IV, an enzyme implicated in the degradation of basement membranes. Using serine proteinase inhibitors and antibodies to plasminogen activators as well as a newly described collagenase inhibitor we demonstrate that a protease cascade leads to the activation of an enzyme(s) that cleaves collagen IV. Inhibition at each step reduces the invasion of the tumor cells through reconstituted basement membrane in vitro. Treatment with a collagenase inhibitor reduced the incidence of lung lesions in mice given i.v. injections of malignant melanoma cells.
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PMID:Effects of inhibitors of plasminogen activator, serine proteinases, and collagenase IV on the invasion of basement membranes by metastatic cells. 283 52

The effects of the antitumorigenic drug estramustine on tumor cell membrane penetration (invasion) were investigated in vitro by utilizing a synthetic basement membrane system (a modified Boyden chamber). Tumor cells were plated on a "partition barrier," consisting of a porous filter (8-micron pores) which was coated with a reconstituted basement membrane matrix (Matrigel), and induced to migrate across the barrier with conditioned medium obtained from 9DU 145 human prostatic tumor cells (passage 9). Quantitative radiolabeling studies demonstrated that specially isolated lines (isolated by several passages through the Matrigel) of DU 145 cells, A2058 melanoma, and B16-F10 melanoma cells were highly invasive such that 15 to 20% migrated across a 1-mm-thick Matrigel layer within 5 h at 37 degrees C. NIH-3T3 cells, mouse fibroblasts, and 20DU 145 cells (passage 20) exhibited little or no membrane invasive behavior. Micromolar concentrations of estramustine (30 to 120 microM) inhibited invasion by the invasive cell lines in a dosage-dependent fashion. Quantitative enzymatic assays and radioimmune assays demonstrated that estramustine inhibited membrane invasion by blocking type IV collagenase secretion. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blots confirmed that 30 to 60 microM estramustine blocked secretion of a Mr 105,000 collagenase protein. Indirect studies showed that a collagenase antibody raised against the Mr 105,000 protein and inhibitors of proteinase activity, including a metalloproteinase inhibitor, and 1,10-phenanthroline, blocked invasion. Because the antibodies inhibited type IV collagenase digestion of 3H-mouse type IV collagen, and invasion simultaneously, it is proposed that collagenolytic activity is involved in invasion. These data demonstrate that estramustine blocks proteinase secretion, and suggest that estramustine may be a useful therapeutic drug for the prevention of metastasis.
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PMID:Blocking of collagenase secretion by estramustine during in vitro tumor cell invasion. 284 50


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