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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

The past decade has witnessed substantial progress in our understanding of the molecular mechanisms of tumor cell interactions with vascular endothelium and extracellular matrix, important events in the metastatic process. This progress has been made possible by the identification and functional characterization of a large number of adhesion molecules involved in tumor cell-vasculature interactions. Essentially, most of the adhesion receptor families so far reported, including integrins, cadherins, selectins, immunoglobulins, and proteoglycans, have been implicated in various stages of tumor progression and metastasis. Disseminating cancer cells often employ ectopic expression of certain adhesion molecules to facilitate their interaction with the vessel wall and matrix, typical examples being the expression of integrins alpha IIb beta 3 and alpha L beta 2 and immunoglobulin family members PECAM-1, ICAM-1, and N-CAM in solid tumor cells. The expression of adhesion molecules in cancer cells and vascular endothelial cells is spatiotemporally regulated, in a dynamic fashion, by a wide diversity of bioactive molecules such as eicosanoid 12(S)-HETE. Recent data indicate that most adhesion molecules, integrins in particular, participate in various signaling functions such as the induction of calcium fluctuation and protein tyrosine phosphorylation. The importance of adhesion molecules in tumor metastasis is also evidenced by their involvement in other important parameters of metastasis such as angiogenesis. Collectively, the accumulated literature suggests that interference with adhesion and signaling represent a future direction for the development of anticancer and antimetastasis therapeutic protocols.
Invasion Metastasis
PMID:Adhesion molecules and tumor metastasis: an update. 765 6

The clinical role of vascularity was examined in metastatic melanoma, analyzing the correlation of the blood vessel density and prognosis. Our study included 51 specimens of metastatic melanoma tissue samples from 31 patients treated with combined chemo-immunotherapy. PECAM-1 (CD31) was used for assessing vascularity by immunohistochemical staining. On the basis of blood vessel counts, patients were classified into 2 main groups: low and high vascularity. A higher blood vessel density was found to be associated with shorter survival, estimated from the primary diagnosis of the disease (38 months), compared with patients with low blood vessel counts (68 months). A similar tendency was observed when vascularity was correlated to the survival period after the detection of the first metastases (13 vs. 30 months) and with survival since the initiation of chemo-immunotherapy (8 vs. 16 months). When vascularity and some common prognostic factors, such as age, sex, DNA ploidy and WHO tumor response, were used for a Cox multivariate analysis, vascularity turned out to be the most significant independent prognostic factor. Our results suggest that counting the blood vessels identified by immunohistochemical staining for the endothelial cell-specific CD31 is a powerful predictor for prognosis in patients with metastatic melanoma and should be considered when selecting patients for therapy.
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PMID:Vascularity and prognosis of metastatic melanoma. 922 13

Cultures of endothelial (En) cells derived from human brain microvessels were established in order to characterize adhesion molecule expression and to assay the adhesion properties of neoplastic cell lines to monolayers of En cells. Low constitutive expression of beta1 integrin (CD29), and ICAM-2 (CD102) was detected on human brain microvessel En cells. The beta1 chain of the VLA integrin family, ICAM-1, E-selectin (CD62E) and VCAM-1 (CD106) but not ICAM-2 and PECAM-1 (CD31) expression was upregulated by IL1-alpha, and TNF-alpha proinflammatory cytokines. High expression of PECAM-1 was found on non-activated human brain EN cells. In order to study the potential role of adhesion molecules in neoplastic cell adhesion two tumor cell lines were chosen. Adhesion of a cell line (DU145) derived from a cerebral metastasis of prostate carcinoma to human brain microvessel En cell monolayers was less pronounced compared to adhesion of a primary prostate carcinoma cell line (ND1). Adhesion of cerebral metastatic neoplastic cell line (DU145) was not significantly influenced by incubation of endothelial cells with different proinflammatory cytokines. The adhesion capability of primary prostate carcinoma line (NDI) was significantly upregulated by TNF-alpha proinflammatory cytokine. Furthermore, the adhesion of ND1 was partly inhibited using anti-E-selectin and VCAM-1 monoclonal antibodies. There was no significant effect of anti-adhesion antibodies on the adhesion characteristics of the cerebral metastatic (DU145) cell line. Our data demonstrate that different mechanisms are involved in the adhesion of neoplastic cells to cerebral En cells and turn our attention to the importance of adhesion molecule expression in the formation of metastases.
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PMID:Influence of adhesion molecule expression by human brain microvessel endothelium on cancer cell adhesion. 972 32

Pentoxifylline (PTX), a methylxanthine derivative widely used as a hemorheological agent in the treatment of peripheral vascular disease, was studied to unveil the mechanisms responsible for its inhibitory action on B16-F10 experimental metastasis. In vitro pretreatment of B16-F10 cells with noncytotoxic concentrations of PTX significantly inhibited their adhesion to reconstituted basement membrane Matrigel(R) and type IV collagen as well as the relative activity of secreted 92 kD metalloproteinase. However, PTX pretreatment of B16-F10 cells did not affect their in vitro invasiveness. Heterotypic organ adhesion assays carried out with B16-F10 cells and suspended organ tissues demonstrated that pretreatment with noncytotoxic concentrations of PTX of both, tumor cells or lung tissue, brought about a dose-dependent inhibition of melanoma cell adhesion to lung. Immunohistochemical studies using antibodies against CD31 adhesion molecule (PECAM-1) revealed that B16-F10 cells adhere to lung endothelial cells. Our results suggest that PTX may exert its inhibitory effect on tumor lodgment, and as a consequence of that on experimental metastases, through an inhibitory action on cell adhesion molecules.
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PMID:Studies on the mechanisms responsible for inhibition of experimental metastasis of B16-F10 murine melanoma by pentoxifylline. 1008 44

Thrombocytopenia was observed in 3 patients with cutaneous angiosarcoma of the scalp and face. A sudden decrease in the platelet count occurred in association with rapid enlargement of primary or metastatic lesions. Neither antiplatelet antibody nor platelet-associated IgG was detected. Increased serum levels of beta-thromboglobulin and platelet factor 4 indicated that platelets were destroyed and consumed within the vascular bed of the tumor. Prominent PECAM-1 expression on tumor cells may be involved in intratumoral platelet aggregation and consumption. We suggest that the sudden development of profund thrombocytopenia in patients with angiosarcoma may suggest either rapid growth of the primary tumor or herald the development of metastatic disease.
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PMID:Cutaneous angiosarcoma with thrombocytopenia. 1032 40

Tumour angiogenesis is essential for tumour growth and metastasis. Several lines of evidence indicate that vascular endothelial growth factor (VEGF) is a major regulator both of physiological and pathological angiogenesis. In this study we assessed the blood vessel density and VEGF expression of 94 melanoma metastases of 70 patients by immunohistochemistry, utilizing antibodies against human platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) and VEGF. The number of blood vessels ranged from 4 to 131 vessels/high power field (HPF), with a mean value of 32 vessels/HPF (+/-21) and a median of 29 vessels/ HPF. Survival since diagnosis of the primary disease and from the start of chemoimmunotherapy, as well as the disease-free survival period, was significantly shorter in the high vascularity group of patients compared with the low vascularity group (P< 0.05 and P< 0.01, respectively). A high overall expression of VEGF in the metastatic melanoma samples was observed. The degree of VEGF expression appeared to have a strong association with the blood vessel density (P= 0.017). This study demonstrates the clinical role of tumour vascularity in the prognosis of patients with metastatic melanoma. In addition, the strong association between vascularity and VEGF expression suggests a crucial role for this growth factor in the neovascularization of metastatic melanoma.
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PMID:Prognostic value of tumour vascularity in metastatic melanoma and association of blood vessel density with vascular endothelial growth factor expression. 1033 35

Adhesion and stabilization of circulating tumor cells to endothelial cells in target blood vessels play an important role in the complex process of metastasis. We examined the cell surface receptors involved in the liver-metastatic adhesive interactions of murine RAW117 large-cell lymphoma cells to unstimulated hepatic sinusoidal endothelial cells (HSE) under physiological flow conditions. Flow cytometric analysis indicated that VCAM-1, ICAM-1 and PECAM-1 are constitutively expressed on the surfaces of both HSE and RAW117 cells. However, monoclonal antibody (mAb) blockade studies showed that ICAM-1 and PECAM-1 affected neither the attachment nor the stabilization step of the adhesion of RAW117 cells to HSE cell monolayers under flow. In contrast, RAW117 cells required a significantly lower shear stress to establish adhesion to HSE cells when VCAM-1 receptors on HSE cells were blocked with mAb. Furthermore, the presence of the anti-VCAM-1 mAb significantly decreased the extent of adhesion compared to that of the control, without affecting adherent cell stabilization times. Blocking the alpha4 integrin subunits present mainly on RAW117 cells produced similar results to those previously observed with anti-VCAM-1 mAb. Although constitutively present mainly on the surfaces of RAW117 cells, MAdCAM-1 and beta7 integrin subunit do not appear to play a role in either the arrest or stabilization of RAW117 cells on HSE cell monolayers. However, blocking the beta1 integrin subunit on the RAW117-H10 cells reduced adhesion to the same extent as anti-alpha4 and anti-VCAM-1 treatments. These observations suggest that an interaction of integrin alpha4/beta1 on RAW117 cells with liver endothelial VCAM-1 occurs during the early stages of the adhesion process and may be important in liver metastasis.
Clin Exp Metastasis 1999
PMID:Integrin alpha4beta1/VCAM-1 pathway mediates primary adhesion of RAW117 lymphoma cells to hepatic sinusoidal endothelial cells under flow. 1091 12

Tumor-stroma interactions are of primary importance in determining the pathogenesis of metastasis. Here, we describe the application of sensitive competitive polymerase chain reaction (PCR) techniques for detection and quantitation of human breast cancer cells (MDA-MB-231) in an in vivo mouse model of experimental metastasis. Human-specific oligonucleotide primers in competitive PCR reactions were used to quantify the amount of MDA-MB-231 cells per tissue per organ. Using this species-specific (semi)quantitative PCR approach, gene expression patterns of (human) tumor cells or (mouse) stromal cells in metastatic lesions in the skeleton or soft tissues were investigated and compared. In all metastatic lesions, MDA-MB-231 cells express angiogenic factors (vascular endothelial growth factors [VEGFs]; VEGF-A, -B, and -C) and bone-acting cytokines (parathyroid hormone-related protein [PTHrP] and macrophage colony-stimulating factor [M-CSF]). In these metastases, PECAM-1-positive blood vessels and stromal cells of mouse origin are detected. The latter express angiogenic factors and markers of sprouting vessels (VEGF receptors flt-1/flk - 1/flk-4 and CD31/PECAM-1). Strikingly, steady-state messenger RNA (mRNA) levels of VEGF-A and -B and the major bone resorption stimulators PTHrP and M-CSF by tumor cells were elevated significantly in bone versus soft tissues (p < or = 0.05, p < or = 0.0001, p < or = 0.001, and p < or = 0.05, respectively), indicating tissue-specific expression of these tumor progression factors. In conclusion, MDA-MB-231 breast cancer cells express a variety of factors in vivo that have been implicated in metastatic bone disease and that correlate with poor survival of patients with breast cancer. We hypothesize that the observed up-regulated expression of angiogenic and bone-resorbing factors by the breast cancer cells in the skeleton underlie the clinically observed osteotropism of breast cancer cells and pathogenesis of osteolytic bone metastases. The application of the species-specific competitive PCR-based assay in vivo can provide new information concerning the involvement of gene families in tumor progression and metastatic disease and greatly facilitates the study of tumor-stroma interactions in cancer invasion and metastasis.
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PMID:Monitoring metastatic behavior of human tumor cells in mice with species-specific polymerase chain reaction: elevated expression of angiogenesis and bone resorption stimulators by breast cancer in bone metastases. 1139 85

We have examined the role of platelet-endothelial cell adhesion molecule-1 (PECAM-1/CD31) during the transendothelial migration of melanoma cells using a novel in vitro system. Comparable studies have suggested the involvement of PECAM-1 in leukocyte transendothelial migration. Such studies have been confirmed using in vivo models of inflammation. These studies prompted us to examine the role of PECAM-1 in tumor cell transendothelial migration. Anti-PECAM-1 monoclonal antibodies, known to block leukocyte transendothelial migration, were tested in co-cultures of human melanoma cells seeded on a monolayer of human lung microvascular endothelial cells. None of these antibodies inhibited the transmigration of melanoma cells. Moreover, confocal microscopy revealed the dissolution of the PECAM-1 adhesion complexes in the endothelial junctions associated with melanoma cells and the lack of PECAM-1 in heterotypic contacts between transmigrating melanoma cells and adjacent endothelial cells. These data, therefore, indicate that PECAM-1 is not required for the transendothelial migration of melanoma cells.
Clin Exp Metastasis 2000
PMID:Platelet-endothelial cell adhesion molecule-1 (CD31) redistributes from the endothelial junction and is not required for the transendothelial migration of melanoma cells. 1159 10


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