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

The expression of integrin laminin receptors was investigated in normal thyroid primary cultures; immortalized normal thyroid cells (TAD-2); papillary (NPA), follicular (WRO), and anaplastic (ARO) thyroid tumor cell lines; seven thyroid tumors (four papillary and three follicular carcinomas); and normal thyroid glands. The expression of alpha1beta1, alpha2beta1, alpha3beta1, alpha6beta1, and alpha6beta4 was found in all tumor specimens and in tumor cell lines, whereas normal thyroid cells and TAD-2 cells lacked the expression of alpha6beta4. Despite the presence of several integrin laminin receptors, adhesion of TAD-2, NPA, and ARO cells to immobilized laminin-1 was poor, whereas WRO cells and follicular carcinoma-derived cells displayed a strong adhesion. Indeed, WRO and follicular carcinoma-derived cells showed expression of a nonintegrin laminin receptor, the 67-kDa high affinity laminin receptor (67LR). TAD-2, NPA, and ARO cells as well as nodular goiter, toxic adenoma, follicular adenoma, and papillary carcinoma-derived cells did not express the 67LR. Adhesion of WRO and follicular carcinoma-derived cells to laminin-1 was specifically inhibited by a recombinant polypeptide containing laminin-binding domains of 67LR, demonstrating that this receptor confers to follicular carcinoma cells attachment capacity to laminin. Moreover, tissue specimens from follicular carcinomas expressed the 67LR, whereas follicular adenomas and normal thyroid tissues were negative. In thyroid tumors, integrin receptors, although abundant, participate weakly in adhesion to laminin. The expression in follicular carcinoma cells of a functional, high affinity 67LR together with nonfunctional integrin LM receptors could be responsible for the tendency of follicular carcinoma cells to metastasize by mediating stable contacts with basal membranes.
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PMID:Laminin receptors in differentiated thyroid tumors: restricted expression of the 67-kilodalton laminin receptor in follicular carcinoma cells. 1037 15

The expression of carbohydrate antigens has been shown by retrospective immunohistochemical analysis to correlate to the progression and metastases of human cancers. However, the mechanisms of these changes of carbohydrate expression and the role of carbohydrates in the malignant behavior of tumor cells are not well known. In this article, we introduce methods to experimentally modify carbohydrate expression in tumor cells and to assess the involvement of these carbohydrate antigens in the malignant behavior of tumor cells. Modifications of the biosynthesis of O- and N-linked carbohydrates, and glycolipids are achieved by treating cultured tumor cells with culture media containing Benzyl-alpha-GalNAc, swainsonine, or D-PDMP, respectively. Enzymatic digestion of cell surface carbohydrates with sialidase, endo-beta-galactosidase or other glycosidases can also be performed. These cells can be used for short term experiments such as adhesion assays. However, modified carbohydrates may be recovered during in vitro and in vivo assays. By transfection of glycosyltransferase cDNA, or selection of tumor cells by binding lectins or antibodies, stable carbohydrate variant cells can be obtained which are suitable for long term experiments such as the experimental formation of metastases in vivo. The biological function of tumor cell surface carbohydrates may be diverse. These molecules are thought to influence adhesion interaction between tumor cells and the endothelial cells of target organs. However, carbohydrate recognition molecules, or lectins, are expressed on a variety of cells in the vascular system and in the immune system. Therefore, it is essential to design appropriate experimental models to study the biological significance of carbohydrate-lectin interactions in cancer progression and metastatic dissemination. Adhesion assays of tumor cells to selectin-transfected CHO cells were performed. Taking molecules other than selectins into consideration, adhesion assays using frozen tissue sections were also performed.
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PMID:[Tumor metastases and adhesion molecules carbohydrates and lectins]. 1041 Jan 58

Mechanisms that regulate the transition of metastases from clinically undetectable and dormant to progressively growing are the least understood aspects of cancer biology. Here, we show that a large ( approximately 70%) reduction in the urokinase plasminogen activator receptor (uPAR) level in human carcinoma HEp3 cells, while not affecting their in vitro growth, induced a protracted state of tumor dormancy in vivo, with G(0)/G(1) arrest. We have now identified the mechanism responsible for the induction of dormancy. We found that uPA/uPAR proteins were physically associated with alpha5beta1, and that in cells with low uPAR the frequency of this association was significantly reduced, leading to a reduced avidity of alpha5beta1 and a lower adhesion of cells to the fibronectin (FN). Adhesion to FN resulted in a robust and persistent ERK1/2 activation and serum-independent growth stimulation of only uPAR-rich cells. Compared with uPAR-rich tumorigenic cells, the basal level of active extracellular regulated kinase (ERK) was four to sixfold reduced in uPAR-poor dormant cells and its stimulation by single chain uPA (scuPA) was weak and showed slow kinetics. The high basal level of active ERK in uPAR-rich cells could be strongly and rapidly stimulated by scuPA. Disruption of uPAR-alpha5beta1 complexes in uPAR-rich cells with antibodies or a peptide that disrupts uPAR-beta1 interactions, reduced the FN-dependent ERK1/2 activation. These results indicate that dormancy of low uPAR cells may be the consequence of insufficient uPA/uPAR/alpha5beta1 complexes, which cannot induce ERK1/2 activity above a threshold needed to sustain tumor growth in vivo. In support of this conclusion we found that treatment of uPAR-rich cells, which maintain high ERK activity in vivo, with reagents interfering with the uPAR/beta1 signal to ERK activation, mimic the in vivo dormancy induced by downregulation of uPAR.
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PMID:Tumor dormancy induced by downregulation of urokinase receptor in human carcinoma involves integrin and MAPK signaling. 1050 58

Adhesion molecules have a number of diverse roles, amongst which is the control of tissue architecture and the maintenance of tissue integrity. Most tumours have an abnormal architecture and loss of tissue integrity is thought to be an important step in the development of local invasion. Thus, alterations in adhesion molecules may have a role in both tumour development and tumour invasion. The role of these molecules in the establishment of tumour metastases is much less certain. The tumour cells in a metastatic deposit are in a different environment and are faced with a different set of selection pressures, which may drive tumour evolution in a new direction. Metastatic deposits often resemble the tumour of origin and not infrequently show better differentiation. Together with evidence from experimental maintenance systems which shows that maintenance of intercellular contact may prevent apoptosis, this implies a role for adhesion molecules in tumour metastasis.
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PMID:Adhesion molecule expression in breast cancer: the phoenix in tumour metastasis? 1064 Sep 87

The adhesion of tumour cells to the hyaluronan (HA) pericellular coat of mesothelial cells is an important step in the peritoneal spread of ovarian cancer. Previously, we have shown that the cell surface molecule CD44 is involved in this process. Paradoxically, the degree of adhesion does not appear to be related to the amount of CD44 expressed. In order to explain this observation we have examined the in vitro adhesion to HA of four high CD44-expressing ovarian cancer lines in relation to their CD44 spliced variant content and the CD44 glycosylation. Adhesion was measured in multiwell plates coated with different concentrations of HA in order to determine both the avidity and the maximum adhesion. Two lines had high adhesion and two lines had low adhesion. The avidity for HA was different for each line, but in all cases this could be totally blocked by treatment with an anti-CD44 antibody. The standard form of CD44 was the major species detected by RT/PCR in all lines and spliced variants were present in low amounts. Neuraminidase treatment increased the adhesion of the 'low-adhesion' lines at all HA coating concentrations; but only substantially increased the adhesion of the 'high-adhesion' lines at the lower HA coating concentrations. Tunicamycin treatment decreased the adhesion of the 'high-adhesion lines' at all HA coating concentrations and only substantially decreased the adhesion of one of the 'low-adhesion' lines when the plates were coated with a low concentration of HA. The adhesion of the remaining 'low-adhesion' line was slightly increased after tunicamycin treatment. It is concluded that glycosylation and not spliced variant content of CD44 affects the adhesive properties of ovarian tumour cells. This conclusion may have important consequences for developing new therapies in ovarian cancer.
Clin Exp Metastasis 1999
PMID:Membrane protein glycosylation and CD44 content in the adhesion of human ovarian cancer cells to hyaluronan. 1084 57

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

Adhesion stabilization of malignant cells in the microcirculation is necessary for successful metastasis formation. The adhesion of colon carcinoma cells to microcirculation extracellular matrix (ECM) components is mediated, in part, by integrins that can be intracellularly linked to cytoskeletal proteins. Thus the functional status of at least certain integrins can be regulated by complex interactions with cytosolic, cytoskeletal and membrane-bound proteins. Wall shear stress caused by fluid flow also influences cellular functions, such as cell morphology, cytoskeletal arrangements and cell signaling. Using a parallel plate laminar flow chamber dynamic adhesion of human HT-29 colon carcinoma cells to collagen was investigated and compared with cell adhesion under static conditions. Cells were pretreated with cytochalasin D, nocodazole, colchicine or acrylamide to disrupt actin filaments, microtubules or intermediate filaments. Disruption of actin filaments completely inhibited all types of adhesive interactions. In contrast, impairment of tubulin polymerization or disruption of intermediate filaments resulted in different effects on static and dynamic adhesion. Treatment with acrylamide did not interfere with dynamic cell adhesion, whereas under static conditions it partially reduced adhesion rates. Under dynamic conditions increased initial adhesive interactions between HT-29 cells and collagen were found after disruption of microtubules, and the adherent cells demonstrated extensive crawling on collagen surfaces. In contrast, under static adhesion disrupting microtubules did not affect cell adhesion rates. Cytochalasin D and acrylamide were found to inhibit Tyr-phosphorylation of FAK and paxillin, whereas microtubule disrupting agents at low but not high concentrations increased phosphorylation of these focal adhesion proteins. Our results revealed that cytoskeletal components appear to be involved in adhesion stabilization of HT-29 cells to ECM components, and hydrodynamic shear forces modulate this involvement. Tyr-phosphorylation of focal adhesion proteins, such as paxillin and FAK, appears to be a part of this cytoskeleton-mediated process.
Clin Exp Metastasis 1999
PMID:Role of the cytoskeleton in adhesion stabilization of human colorectal carcinoma cells to extracellular matrix components under dynamic conditions of laminar flow. 1091 16

Adhesion stabilization is a prerequisite for the long-term adhesion of circulating metastatic tumor cells, and tumor cells with different metastatic potential demonstrate distinct patterns of cell adhesion properties. An important event during formation of organ metastases is integrin-mediated extracellular matrix (ECM) binding that can initiate signal transduction events. Recently we reported that Ser/Thr kinases are involved in regulation of tumor cell adhesion. In the present study the influence of dephosphorylation by Ser/Thr protein phosphatases (PPases) on tumor cell adhesion was investigated. Pretreatment of poorly and highly metastatic human HT-29 colon carcinoma cells with the broad-range inhibitors sodium fluoride (NaF) and sodium pyrophosphate (PyroP) resulted in strong reduction in adhesion of HT-29 cells to various ECM components. Surprisingly, when specific Ser/Thr PPase inhibitors like tautomycin were used we found only a partial reduction in adhesion of highly metastatic HT-29LMM cells to collagen I but not to collagen IV. Other inhibitors did not inhibit adhesion, and poorly metastatic HT-29P were not affected by any specific Ser/Thr PPase inhibitors. Therefore, the effects of NaF on adhesion-mediated Tyr phosphorylation were investigated further. Pretreatment with this inhibitor led to a reduction in phosphorylation of focal adhesion kinase (FAK). In contrast, in cells grown adherent to tissue culture dishes, low concentrations of NaF increased FAK phosphorylation whereas high concentrations inhibited the amount of phosphorylated FAK. Although NaF inhibited adhesions it did not cause changes in cell morphology or detachment of cells from ECM. We hypothesize that dual-specific PPases may be involved in the regulation and establishment of new adhesive interactions in HT-29 cells, but they are not required for maintenance of stable adhesions to ECM.
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PMID:Time-dependent dephosphorylation through serine/threonine phosphatases is required for stable adhesion of highly and poorly metastatic HT-29 colon carcinoma cell lines to collagen. 1095 84

Bowel injuries, which may occur as a result of the insertion of an insufflation needle or trocar, are a rare complication of laparoscopy. They are generally recognized either immediately or a few days after the operation. We present a case of laparoscopic perforation of the small intestine in a patient who had undergone previous pelvic surgery for an ovarian carcinoma. On ultrasound (US), the patient had multiple hepatic lesions resembling hepatic metastases. To confirm the diagnosis, laparoscopy with guided liver biopsy was performed on the grounds that this procedure is regarded as more appropriate than CT- or US-guided hepatic biopsy. Veress needle and trocar insertion were performed at a proper distance from the abdominal scar. However, the abdominal cavity was not visible after the trocar's insertion due to the unexpected presence of adhesions. This precluded the continuation of the procedure. In the following days, the patient experienced only mild abdominal discomfort. However, 2 weeks after laparoscopy, the patient presented signs of peritoneal reaction and underwent laparotomy. Adhesion-fixing jejunal loops to the anterior abdominal wall were discovered at the site of the trocar puncture. Moreover, two hiatuses of these loops were observed and sutured. The follow-up was uneventful. As this case illustrates, laparoscopic bowel injuries remain an unpredictable event. Recognition of this complication may occur several days after the procedure, as the tamponating effect of adhesions on the jejunal hiatus delays the involvement of the peritoneum.
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PMID:Delayed recognition of inadvertent gut injury during laparoscopy. 1128 88

Recent advancement in the research of malignant melanoma is reviewed. Among many gene alterations detected in human melanoma, defect of CDKN2A located at chromosome 9p21 seems to be most important in the earlier developmental phase, though significance of this gene in the evolution of melanoma in situ has not been confirmed yet. Deletions of PTEN/MMAC1 on 10q23.3 and AIM1 on 6q21 as well as mutations of ras gene are involved in the later progression stages of melanoma. Adhesion molecules relevant to development and progression of melanoma have been intensely investigated in recent years, revealing crucial roles of cadherins and alpha(v)beta(3) integrin in the biologic behaviors of melanoma cells. Melanoma is characterized by extremely high potential of developing metastases. Dynamic changes of matrix metalloproteinase activity during invasion and movement of melanoma cells may be a major concern in this field. Fragility of blood vessels in melanoma lesions is another important point related to hematogeneous metastases. Acral lentiginous melanoma is a unique subtype of melanoma, because, in contrast to other subtypes, ultraviolet irradiation is not a major factor in its development. Investigation of pathogenesis of acral lentiginous melanoma surely provides us with new information about mechanism of melanocyte transformation. Recent advances in the management of malignant melanoma are also briefly reviewed, such as biochemotherapy, immunotherapy, and gene therapy. Finally, the concept of molecular classification of melanoma by gene expression profile is introduced, which possibly enables us to give the tailor-made therapy for each melanoma patient in the near future.
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PMID:Recent advances in melanoma research. 1132 15


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