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

Small cell lung cancer (SCLC) is a fatal malignancy due to its propensity to metastasize widely and to reoccur after chemotherapy in a drug-resistant form. While most SCLC cell lines are anchorage independent for growth, laminin induced the attachment of five of six SCLC cell lines tested (NCI-N417, NCI-H345, NCI-H146, NCI-H187, NCI-H510, and NCI-H209). NCI-N417 SCLC cells adopted a flattened morphology on laminin, and a classic SCLC cell line (NCI-H345) demonstrated a neuron-like appearance while the other SCLC cell lines except NCI-H187 cells, attached but did not spread. Adhesion to laminin was associated with increased resistance to several cytotoxic drugs. Matrigel, an extract of basement membrane proteins, greatly accelerated tumor growth when coinjected with SCLC cells in athymic mice. A synthetic peptide from the B1 chain of laminin, cyclic-YIGSR (Tyr-Ile-Gly-Ser-Arg), inhibited laminin-induced SCLC cell adhesion and migration in vitro and reduced the size of the tumors they formed when coinjected with matrigel and YIGSR. These results suggest that the interaction of SCLC cells with laminin and possibly with other basement membrane proteins can enhance their tumorigenicity and drug resistance.
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PMID:Reconstituted basement membrane (matrigel) and laminin can enhance the tumorigenicity and the drug resistance of small cell lung cancer cell lines. 216 54

In vitro attachment assays were carried out to assess adhesion between two basement membrane proteins, type IV collagen and laminin, and rat rhabdomyosarcoma (RMS) cell lines with different metastatic potentials. Whereas cells did not adhere to type IV collagen, adhesion to laminin appeared to be very sensitive as maximal adhesion was achieved in dose-response assays with only nanograms of laminin. Adhesion was mediated by interactions between coated laminin and cell surface components, probably receptors, but not endogenous laminin. Laminin-mediated adhesion of RMS cell lines was compared with that of the MCF-7 (human mammary carcinoma) and the L6 (rat myoblast) cell lines. In dose-response assays, RMS cell lines required 10 times less laminin to reach half-maximal attachment rates than MCF-7 and L6 cell lines. Two laminin fragments, P1 and E8, which are structurally and immunologically distinct as shown by alpha-helix content, SDS-PAGE and monoclonal antibody mapping, supported adhesion by RMS cells and L6 myoblasts, but MCF-7 adhered only to P1. This fragment was 10 times less active than laminin in RMS cell lines. Attachment in dose-response assays and adhesion inhibition studies by antibodies revealed that E8 accounted for the activity of laminin in RMS cell adhesion. Adhesion in the RMS cell lines was dominated by interaction with E8 regardless of metastatic potential.
Clin Exp Metastasis
PMID:Laminin-mediated adhesion in metastatic rat rhabdomyosarcoma cell lines involves prominent interactions with the laminin E8 fragment. 252 68

In order to study the effect of estrogens and antiestrogens on the adhesive properties of human breast cancer cells, the attachment on endothelial cells (EC), on subendothelial extracellular matrix (ECM) and on ECM components (collagen I and IV, laminin, fibronectin) of estrogen-dependent (MCF-7, ZR75-1) and estrogen-independent (BT-20) breast cancer cell lines was investigated. The cells were grown under conditions of controlled exposure to estrogen [17 beta-estradiol (E2)] and/or antiestrogens [tamoxifen (Tam) or 4-hydroxytamoxifen (OH-Tam)]. Treatment by E2 enhanced the ability of ZR75-1 cells to adhere to the various substrates, which contrasts with the observed absence of effects with the BT-20 cells. Similarly, Tam or OH-Tam induced a reduction of the adhesion of ZR75-1 tumor cell, but not of BT-20 cells. This effect was reversed by competing concentrations of E2. The effects on MCF-7 cell adhesion were similar to those described for ZR75-1 cells, but could not be reproducibly observed. Adhesion assays carried out with ZR75-1 cells grown in the absence or presence of phenol red, a pH indicator which behaves as a weak estrogen, led to a similar pattern of cell attachment. Conditioned media harvested from E2- or Tam-treated ZR75-1 cells failed to induce any effect on adhesion of other ZR75-1 cells grown in E2-deprived medium, suggesting that secretory activities are not required for the control of cell adhesiveness. The results suggest that estrogens and antiestrogens can control the adhesive behavior of breast tumor cells through their hormone responsive structures possibly by regulating expression of cell adhesion proteins and/or their cell surface receptors.
Clin Exp Metastasis
PMID:Modulation of human breast cancer cell adhesion by estrogens and antiestrogens. 270 28

Adhesion variants can be isolated from suspension growing highly metastatic murine ESb tumor cells under reproducible conditions from uncloned as well as from cloned ESb tumor cells. One such variant, ESb-MP, has been analyzed in detail. In vitro it had similar growth properties and high invasive capacity as the parental ESb cells. In vivo, ESb-MP cells showed a reduced growth capacity as compared to ESb cells. This was seen at the site of tumor cell transplantation (increased latency period) as well as at the site of secondary tumor growth in internal organs. ESb-MP tumor cells disseminated much later than ESb cells from the primary tumor into the blood stream. Both tumor lines metastasized to the liver but they affected liver functions in a different way: ESb cells infiltrated the liver diffusely and exerted toxic effects on liver parenchyma very quickly. This resulted in early increase of liver enzyme activity in the blood. In contrast, liver infiltrated by ESb-MP cells showed a more focal type of colonization and the organs seemed to be functioning for much longer periods. In fact, animals inoculated with ESb-MP cells subcutaneously or intravenously had an increased life expectancy compared to ESb-tumor-bearing animals of about 300%. The organotropism of both tumor lines remained similar although there were kinetic and quantitative differences, especially with regard to the kidney. In late stages of tumor growth, ESb-MP-tumor-bearing animals developed a high percentage of metastases in the kidney and around and within the spinal cord, thereby causing a syndrome of hind-leg paralysis. This syndrome was remarkable in its reproducibility, especially after intravenous tumor cell inoculation. The changed adhesiveness thus seemed to have affected the tumor latency period, the speed of dissemination into blood and internal organs, the mode of organ infiltration (focal vs. diffuse) and of metastatic growth, parameters which all might contribute to the greatly reduced overall malignancy.
Invasion Metastasis 1988
PMID:Changes in tumor cell adhesiveness affecting speed of dissemination and mode of metastatic growth. 325 67

Clinical and experimental observations suggest that tumor-induced endothelial cell (EC) injury may be one of several initial events in the establishment of tumor metastases. This work investigates tumor-induced EC injury and the interaction between tumor-damaged EC and platelets. We used cultured bovine EC and extracts of four cultured human malignancies. EC injury was assessed by 51Cr and lactic dehydrogenase (LDH) release. Incubation of EC with melanoma, breast carcinoma or lung carcinoma caused significant LDH and 51Cr release, whereas colon cancer seemed ineffective. Increased adhesion of platelets to tumor-injured EC was noted. These observations indicate that certain varieties of tumor cause EC injury. Adhesion of platelets to tumor-injured EC results in the formation of platelet-tumor thrombi at the endothelial surface, an event that may initiate tumor invasion of the vessel wall.
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PMID:Tumor interaction with vascular endothelium. 366 82

Lewis lung carcinoma cells are able to bind sugar residues, mainly alpha-D-glucosyl and alpha-D-mannosyl derivatives as assessed by fluorescent neoglycoproteins binding assay. We have investigated the binding efficiency and shown that: 3LL tumor cells are heterogeneous with regards to their capability to recognize neoglycoproteins, as shown by fluorescence microscopy and flow cytofluorometry analyses; basically two distinct subpopulations could be evidenced which were called glucose-receptor-rich (or glucose-specific lectin-rich, GLR 3LL) and glucose-receptor-poor (or glucose-specific lectin-poor, GLP 3LL) cells; those two subpopulations could be separated on the basis of their binding properties to neoglycoprotein-substituted microcarriers onto which GLR 3LL cells were able to rapidly adhere (2 h) while GLP 3LL cells were not. Some aspects of the biological behavior of these two selected populations were investigated in order to determine the possible involvement of 3LL cell membrane sugar receptors in cell-cell recognition and adhesion to other cells: namely C57 B1/6 mouse pulmonary cells maintained in primary culture. The two 3LL sublines bind to pulmonary cells but their adhesion kinetics were markedly different. Adhesion inhibition studies showed the adhesion process to be dependent upon the specificity of membrane lectins present on both the tumor cell surface (alpha-D-glucose-specific) and on the pulmonary cells (alpha-L-fucose-specific). Surface sugar-specific receptors on mouse pulmonary cells were shown to bind beta-D-galactose-, alpha-L-fucose and alpha-L-rhamnose substituted serum albumin. A neoglycoprotein bearing alpha-L-rhamnose residues was an efficient binder under the conditions of cell adhesion experiments and a potent cell adhesion inhibitor. A fucose-containing neoglycoprotein was shown to have a high inhibitory activity when used concomitantly to alpha-D-glucose-containing neoglycoproteins. Adhesion inhibition experiments, performed with cells the sugar specific receptors of which have been selectively inactivated, showed that the alpha-L-fucose specific receptors on pulmonary cell surface are partly responsible for the specificity of this cell-cell recognition process.
Invasion Metastasis 1986
PMID:Involvement of membrane sugar receptors and membrane glycoconjugates in the adhesion of 3LL cell subpopulations to cultured pulmonary cells. 380 41

By implantation of BSp73 ascites cells in a subcutaneous site and subsequent subcutaneous passage of either the local tumor node or metastatic lung tissue, variants were obtained which differed with respect to morphology and to metastatic capacity. The highly metastasizing variant ASML showed spherical morphology in culture, while the nonmetastatic variant AS showed adhesion and spreading. Upon cloning it was observed that colonies with fully expressed morphotypes were readily obtained from solid tissue of both variants. Parental ascites as well as the tumor line derived from the primary solid tumor gave rise to stable expression of either morphotype only after prolonged culturing. Mixing of established clones did not result in an interclonal adaptation of growth rates in vivo. Further characterization of variants AS and ASML revealed marked differences in the outer cell surface. Adhesion of AS cells onto plastic was found to be mediated by fibronectin, laminin and 4 out of 5 collagen types. ASML cells showed adhesion only with collagen type III at higher concentrations. Cytogenetic analysis revealed that the adaptation of BSp73 cells to ascitic growth ultimately led to an increase in chromosome numbers, and this was conserved in ASML cells (modal number 63, range 49-74). AS cells on the other hand showed a modal number of 47 (range 45-49). The chromosome count distribution was rather narrow in ascites cells in vivo, but it was very broad in clones derived thereof, indicating that diversity was obtained in culture rather than in vivo. The data are compatible with the assumption that the nonmetastatic variant was not preexisting in BSp73 ascites but represents a stable phenotype which infrequently arises in a particular microenvironment by chromosome loss from a hyperdiploid parental population.
Invasion Metastasis 1985
PMID:Clonal analysis of diversity in the BSp73 rat tumor. 406 7

Adhesion in vitro is described in cells from a tumor pair originating from a single methylcholanthrene-induced mouse carcinoma. One member of this tumor pair shows a high incidence of metastases while the other does not metastasize. Cells from the non-metastasizing carcinoma were found to form close and focal contacts with a glass substrate consecutively, as do normal mouse kidney epithelial cells. Cells from the metastasizing carcinoma, however, had only limited areas of close contact and generally failed to form focal contacts. It is suggested that this alteration in cell-substrate adhesion contributes to the release and mobility of metastatic cells.
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PMID:Adhesion of metastatic and non-metastatic carcinoma cells to glass surfaces. 723 23

Interactions between tumour cells and the endothelium are vital to the formation of haematogenous metastases. Binding to model endothelium of one oestrogen receptor positive breast carcinoma cell line (MCF-7) and one receptor negative line (HS578T) was examined in vitro together with endothelial retraction induced by these tumour cells. Adhesion was inhibited by monoclonal antibodies specific for the VLA integrins and by peptides containing the RGD motif which is commonly recognised as a ligand by the VLA adhesion molecules. However, binding of the two tumour cell lines was inhibited by monoclonal antibodies specific for different VLA molecules; anti-alpha 6 beta 1 inhibited MCF-7 adhesion but anti-alpha 5 beta 1 inhibited Hs578T. These results were consistent with flow cytometric quantification of the expression of these VLA integrins on the surfaces of the two tumour cell lines. Enzyme-linked immunosorbent assays (ELISA) demonstrated that laminin was present on the endothelial cell surface but collagen IV was absent. ELISA failed to detect increased exposure of the subendothelial matrix during the first hour after addition of either cancer cell type. This was supported by assays which demonstrated maintenance of the endothelial permeability barrier during this period. Slight endothelial retraction was detected within 2 hours of the addition of tumour cells. It is concluded that binding between tumour cells and confluent endothelium is inhibited by the blockade of adhesion molecules which are normally associated with interactions between the cell and the subendothelial matrix. Tumour cell to matrix interactions rather than direct tumour to endothelial cell adhesion may be the limiting step in tumour cell binding to the endothelium.
Clin Exp Metastasis 1995 May
PMID:The role of beta 1 integrins in adhesion of two breast carcinoma cell lines to a model endothelium. 753 54

Cell adhesion and migration are important features in tumor invasion, being mediated in part by integrins (extracellular matrix receptors). Integrins are significantly decreased in human prostate cancer. An exception is alpha 6 integrin (laminin receptor) which persists during prostate tumor progression. We have selected high (DU-H) and low (DU-L) expressors of alpha 6 integrin from a human prostate tumor cell line, DU145, to assess experimentally the importance of alpha 6 integrin in tumor invasion. DU-H cells exhibited a four-fold increased expression of alpha 6 integrin on the surface compared to DU-L cells. Both cell types contained similar amounts of alpha 3 and alpha 5 integrin. The DU-H cells contained alpha 6 subunits complexed with both the beta 1 and beta 4 subunits whereas DU-L cells contained alpha 6 complexed only with beta 4. DU-H cells were three times more mobile on laminin as compared to DU-L, but adhered similarly on laminin. Adhesion and migration were inhibited with anti-alpha 6 antibody. Each subline was injected intraperitoneally into SCID mice to test its invasive potential. Results showed greater invasion of DU-H compared to DU-L cells, with increased expression of alpha 6 integrin on the tumor at the areas of invasion. These data suggest that alpha 6 integrin expression is advantageous for prostate tumor cell invasion.
Clin Exp Metastasis 1995 Nov
PMID:Integrin alpha 6 expression in human prostate carcinoma cells is associated with a migratory and invasive phenotype in vitro and in vivo. 758 6


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