Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro, tumor-selective Hsp70 plasma membrane localization correlates with increased sensitivity to lysis mediated by a subpopulation of human natural killer (NK) cells that adhere to plastic following cytokine stimulation. In the present study, we analyzed the capacity of adoptively transferred human NK cells in SCID/beige mice for local tumor control and prevention of metastatic dissemination of Hsp70-expressing CX(+) and non-expressing CX(-) tumors following orthotopic (o.t.) injection. Both tumor sublines were derived by cell sorting of the original cell line, CX2, and thus exhibit an identical MHC and adhesion molecule expression pattern but differ with respect to Hsp70 plasma membrane expression. Viability of adherent, human NK cells in SCID/beige mice up to 18 days and the capacity to migrate have been demonstrated. Growth of Hsp70-expressing and non-expressing CX(+) and CX(-) tumor cells was completely suppressed when 10 x 10(6) NK cells were injected into the i.p. cavity on day 4 after inoculation of 2.5 x 10(6) tumor cells. Although a single injection of 5 or 2.5 x 10(6) NK cells was not sufficient to suppress tumor growth completely in all mice, the reduction in size of CX(+) tumors was significantly greater than that of CX(-) tumors. To mimic the clinical situation, ex vivo stimulated NK cells were injected i.v. on day 4 after o.t. injection of tumor cells. Under these conditions, growth of Hsp70-expressing primary tumors and metastases was suppressed. If CX(-) tumor cells were injected, 3 of 9 mice developed Hsp70-negative primary tumors. However, none of these mice developed distant metastases. In summary, our data indicate that Hsp70 acts as a recognition structure for adherent NK cells in a SCID/beige mouse model.
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PMID:Adoptive transfer of human natural killer cells in mice with severe combined immunodeficiency inhibits growth of Hsp70-expressing tumors. 1107 50

CD31, an adhesion molecule expressed by endothelial cells, leukocytes, and platelets, is used in surgical pathology as a marker of normal and neoplastic vascularization. During the assessment of angiogenesis in breast carcinomas, CD31 expression was observed in a single case of large (5.2 cm diameter) high nuclear grade ductal carcinoma in situ (HG-DCIS) associated with poorly differentiated invasive ductal carcinoma (G3-IDC). Expression was limited to the cell membrane. This study focused on 32 HG-DCIS> or = 2 cm, either pure or associated with IDC. Cancer cells wereCD31(+) in 11 cases. Double staining using anti-CD31 monoclonal antibody (MAb) and anti-CD44 MAb, the anti-hyaluronate receptor, showed that foci of CD31(+) and CD44(-) tumour cells could be traced throughout the glandular tree, marking the intraductal diffusion of tumour up to Paget's cells at the nipple. The associated G3-IDC and their lymph node metastases were instead CD31(+) and CD44(+). CD31(+) tumours were oestrogen receptor (ER)(-), frequently p53(+) and c-erb-B2(+), and infiltrated by CD4(+) T lymphocytes. Normal and hyperplastic epithelia were constantly CD31(-). Other endothelial markers (e.g Factor VIII-RA and CD34) were not expressed by carcinoma cells, as was CD38, the CD31 ligand. In conclusion, CD31 expression is a feature acquired by breast cancer cells in the DCIS model. CD31 expression mainly correlates with tumour cells spreading within the ductal system. Finally, the invasive phenotype requires the co-expression of CD31 and CD44.
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PMID:Expression of CD31 by cells of extensive ductal in situ and invasive carcinomas of the breast. 1185 2

E-cadherin is a calcium 2+-dependent cell-adhesion molecule that determines epithelial development in the embryo and maintains adult differentiated epithelium and homeostasis. Aberrant or decreased expression has been reported to be associated with prostate carcinoma progression. The degree of E-cadherin expression in prostate cancer remains controversial. Some studies have reported decreased expression of E-cadherin as tumors advance and metastasize. Other studies have not demonstrated this relationship. To address these variations, we undertook a study to systematically evaluate E-cadherin expression in a broad range of prostate tissue. Benign prostate, clinically localized prostate cancer, and hormone-refractory metastatic prostate cancer were analyzed under uniform conditions using high-density tissue microarrays (TMA). Formalin-fixed, paraffin-embedded prostate carcinoma from men with clinically localized prostate carcinoma and autopsy material from men who died of widely metastatic, hormone-refractory prostate carcinoma were arrayed into 6 high-density TMA blocks. Benign and atrophic prostate tissue and high-grade prostatic intraepithelial neoplasia (PIN) were also included from the clinically localized cases. Immunohistochemistry was performed using the immunoglobulin G1 mouse monoclonal antibody (HECD-1; Zymed, San Francisco, CA). Membranous staining was recorded as low (aberrant) or high (normal). E-cadherin expression was considered aberrant if less than 70% of the cells had strong membranous staining. A total of 1,220 prostate TMA samples were analyzed. High (normal) E-cadherin expression was seen in 87% of 757 benign, 80% of 41 high-grade PIN, 82% of 325 prostate carcinoma and 90% of 97 hormone-refractory prostate carcinoma TMA samples. Mean E-cadherin expression was determined for each of the 128 clinically localized prostate cancer cases. Aberrant E-cadherin expression showed a statistical trend toward an association with positive surgical margins (P =.012), higher Gleason score (P =.18), and prostate-specific antigen (PSA) failure (Kaplan-Meier analysis, log-rank P =.09). There was a statistically significant association between aberrant E-cadherin expression and larger tumor size (P =.01). No significant associations were seen with extraprostatic extension and seminal vesicle invasion. The current study shows a broad-spectrum approach to evaluating E-cadherin protein expression in prostate carcinoma. Clinically localized prostate tumors, treated with surgery alone, show a high level of E-cadherin expression. Aberrant expression was identified in tumors with positive surgical margins, higher Gleason score, and a higher rate of PSA failure. However, these trends were not statistically significant. A statically significant association between aberrant E-cadherin expression and larger tumor size was identified. In the metastatic hormone-refractory prostate tumors, E-cadherin expression was vastly expressed, and only rare cases had aberrant expression. Therefore, the findings of this study are most consistent with a transient down-regulation of E-cadherin in localized prostate cancer. Metastatic prostate cancer shows strong E-cadherin expression as determined by anti-E-cadherin antibody HECD-1.
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PMID:E-cadherin expression in prostate cancer: a broad survey using high-density tissue microarray technology. 1148 67

Tumor metastasis involves many stage-specific adhesive interactions. The expression of several cell adhesion molecules, notably the integrin alpha(v)beta(3), has been associated with the metastatic potential of tumor cells. In this study, we used a novel in vitro assay to examine the role of alpha(v)beta(3) in the transmigration of melanoma cells through a monolayer of human lung microvascular endothelial cells. Confocal microscopy revealed the presence of the integrin alpha(v)beta(3) on melanoma membrane protrusions and pseudopods penetrating the endothelial junction. alpha(v)beta(3) was also enriched in heterotypic contacts between endothelial cells and melanoma cells. Transendothelial migration of melanoma cells was inhibited by either a cyclic Arg-Gly-Asp peptide or the anti-alpha(v)beta(3) monoclonal antibody LM609. Although both platelet endothelial cell adhesion molecule-1 and L1 are known to bind integrin alpha(v)beta(3), only L1 serves as a potential ligand for alpha(v)beta(3) during melanoma transendothelial migration. Also, polyclonal antibodies against L1 partially inhibited the transendothelial migration of melanoma cells. However, addition of both L1 and alpha(v)beta(3) antibodies did not show additive effects, suggesting that they are components of the same adhesion system. Together, the data suggest that interactions between the integrin alpha(v)beta(3) on melanoma cells and L1 on endothelial cells play an important role in the transendothelial migration of melanoma cells.
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PMID:Involvement of integrin alpha(v)beta(3) and cell adhesion molecule L1 in transendothelial migration of melanoma cells. 1155 9

The purpose of this study was to assess the prognostic influence of beta-catenin expression by immunohistochemistry in patients with cervical adenocarcinomas. The study group comprised of 51 patients who underwent total hysterectomy for cervical cancer. The median follow-up was 39 months (range 1-138 months). beta-catenin was expressed strongly on the membranes of normal cervical epithelial and glandular cells. Uniform membranous beta-catenin staining localized to intercellular borders was observed in 35% of tumors, whereas 65% of tumors demonstrated an abnormal pattern of reduced or aberrant beta-catenin expression (i.e., cytoplasmic and/or nuclear staining patterns). Abnormal beta-catenin immunoreactivity was associated statistically with advanced pathologic stage (p=0.018). The 10-year disease-free survival was 51.0% in patients with preserved expression of beta-catenin. On the other hand, a poorer prognosis was noted in the group with abnormal expression of beta-catenin with a 10-year disease-free survival of 43.4%. By multivariate analysis, low pathologic stage (stages I and II, p=0.001) and preservation of beta-catenin expression (p=0.012) were independently favorable prognostic factors. Our results indicate that changes in beta-catenin expression occur during the progression of cervical adenocarcinoma to an invasive phenotype. These results suggest that beta-catenin is an important intercellular adhesion molecule. Assessment of beta-catenin immunoreactivity may be a useful prognostic tool in cervical adenocarcinoma complementary to established prognostic factors. Furthermore, we developed a strategy for choosing biomarkers representing the steps in malignant progression in an effort to identify patients with occult metastases who will need adjuvant therapy and spare women from unnecessary interventions.
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PMID:Beta-catenin expression as a prognostic indicator in cervical adenocarcinoma. 1156 71

The complex process of tumor invasion requires the coordinated expression and activity of cell-substratum adhesive interactions and of cell-associated protease systems, which destroy the extracellular matrix (ECM), in order to enable the invading cells to simultaneously grip and destroy the anatomical barriers that control cell spreading. A number of data indicate that such a 'grip and go' process may be performed by an enlarging series of cell membrane-associated serine proteases and serine protease receptors, which provide the invasive cells with a functional unit (the protease and its receptor), able to mediate cell-substratum adhesion through specific receptor domains, to proteolytically degrade ECM and to deliver into the cell signals that up-regulate the expression either of the protease/receptor complex, or of other adhesion molecules, such as integrins. There is evidence that some proteases and protease receptor expression are under the control of tumor hypoxia, which is the result of an imbalance in oxygen supply and demand. The urokinase-type plasminogen activator (u-PA) receptor (u-PAR) is under hypoxic control and cooperates with other serine proteases of the blood coagulation pathways that may extravasate in the tumor milieu as a result of hypoxia-simulated increase of vessel permeability. Other serine proteases and their receptors cooperate with the cell-associated fibrinolytic system to promote cell invasion. Among these, tissue factor and its ligand coagulation factor VII, thrombin and its protease-activated receptors, and type II trans-membrane serine proteases seem to play a crucial role. This Review takes into consideration the complex scenario of the single serine proteases and related receptors that are involved in cell invasion, as well as the protease receptor/adhesion molecule interplay which is necessary to focus the cell surface-driven proteolysis where adhesion provides a grip to the invading cell.
Clin Exp Metastasis 2002
PMID:Multiple pathways of cell invasion are regulated by multiple families of serine proteases. 1206

The expression of adhesion molecules on endothelial cells as well on tumor cells regulates and directs adhesion and transmigration of tumor cells through the endothelial cell barrier as one prerequisite to the formation of metastasis. Thy-1 is an inducible activation-associated cell-adhesion molecule on human dermal microvascular endothelial cells (HDMECs). In this study we investigated whether the Thy-1/Thy-1 ligand interaction may also play a role in adhesion of melanoma cells to endothelial cells. In situ, a strong Thy-1 expression on endothelial cells in melanoma and melanoma metastases was observed. In vitro, Thy-1 expression was stimulated by melanoma-cell-derived soluble factors, reflecting that Thy-1 expression in melanoma is not only due to a nonspecific inflammatory response. TNFalpha and bFGF were not responsible for this effect. In vitro and in situ a Thy-1 ligand was detected on melanoma cells. In cell-adhesion assays we showed the involvement of the Thy-1/Thy-1 ligand interaction in adhesion of melanoma cells to HDMECs. In summary, the data support that the study of the Thy-1/Thy-1 ligand interaction might give a more detailed insight into the regulation and direction of adhesion of melanoma cells to endothelial cells as one critical step in the formation of tumor metastasis.
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PMID:The Thy-1/Thy-1 ligand interaction is involved in binding of melanoma cells to activated Thy-1- positive microvascular endothelial cells. 1207 34

Invasiveness and the capacity of tumor cells to form distant metastases are important cellular characteristics associated with a poor prognosis in breast cancer patients. In an approach to find genes that are potentially involved in these processes, RNA species showing different abundance in RNA pools from 12 invasive and 13 noninvasive mammary carcinoma-derived cell lines have been identified by hybridization to cDNA microarrays. CD24, keratin 19, keratin 8, GOB-4 and ezrin-radixin-moesin-binding phosphoprotein 50 were found to be preferentially expressed by noninvasive cells whereas vimentin was confirmed as a characteristic of invasive cells. Only differences in expression higher than 3-fold evident in three independent hybridization experiments were considered significant. For all cell lines, expression of mRNA coding for the adhesion molecule CD24, previously suggested to play an important role during tumor progression to more invasive phenotypes, has been quantified by real-time RT-PCR. Flow-cytometric analyses confirmed that CD24 mRNA reflects the amount of cell surface CD24 (Spearman R = 0.88, p = 10(-6)). CD24 mRNA was found to be absent or weakly expressed in 9/12 (75%) invasive cell lines compared to 3/13 (23%) noninvasive cell lines. The correlation between CD24 expression and invasiveness was calculated to be highly significant with chi2 = 6.74 and p = 0.0094. Future analyses of primary breast carcinomas are warranted to define the role of CD24 in future diagnostic and therapeutic approaches.
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PMID:Expression profiling of mammary carcinoma cell lines: correlation of in vitro invasiveness with expression of CD24. 1221 94

Pulmonary metastases occur in 3% to 8% of all cases of colorectal cancers. Therefore, we evaluated prognostic factors and examined the correlation between the expression of adhesion molecule CD44 variant 9 and the pulmonary metastasis from colorectal cancer. Of 512 patients with colorectal cancers, clinicopathological findings, prognoses, and prognostic factors were evaluated in 42 patients with pulmonary metastases (8%), together with the expression of adhesion molecule CD44 variant 9 by immunohistochemical staining with monoclonal antibody prepared in our department. It was found that the presence or absence of extrapulmonary metastasis, treatment by pulmonary resection, and serum carcinoembryonic antigen levels were prognostic factors. The 5-year survival rate was 35% in patients who underwent pulmonary resection. In addition, adhesion molecule CD44 variant 9 was expressed in the primary colorectal cancers in 89 (42%) of 213 patients without hematogenous metastases and 23 (88%) of 26 patients with pulmonary metastases. Therefore, the rate of CD44 variant 9 expression in the primary colorectal cancer tissues was significantly higher in patients with pulmonary metastases from colorectal cancers. Among patients with pulmonary metastases from colorectal cancers, long-term survival was achieved in those without extrapulmonary metastases, because metastatic tumors in the lungs were completely removed by pulmonary resection. In addition, the abnormal expression of adhesion molecule CD44 variant 9 in the primary colorectal cancer is partly responsible for pulmonary metastasis.
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PMID:Evaluation of clinicopathological factors and the correlation between the adhesion molecule CD44 variant 9 expression and pulmonary metastases from colorectal cancers. 1222 16

The expression of the following cell adhesion molecules, their beta1 and beta2 integrin ligands and the cytokine tumour necrosis factor-alpha (TNF-alpha) was investigated by light and electron microscope immunohistochemistry in the liver tissue in 20 patients with colorectal and gastric cancer also presenting with liver metastases: intercellular adhesion molecule-1 (ICAM-1), vascular endothelial adhesion molecule-1 (VCAM-1), E-selectin, leucocyte function-associated antigen-1 (LFA-1), macrophage antigen-1 (Mac-1), and very late antigen-4 (VLA-4). We have found a parallel enhancement of the adhesion molecules and of TNF-alpha in liver sinusoids surrounding metastases. The expression of ICAM-1 was enhanced on sinusoidal cells in all zones of the acinus. VCAM-1 immune reactivity was diffuse but less intensive in the lobule. E-selectin expression was observed in sinusoidal cells attached to metastases. In tumour metastases the expression of ICAM-1, VCAM-1, and E-selectin was visible on the tumour vascular endothelium. Tumour infiltrating host cells sowing positive immunoreactivity for ICAM-1, VCAM-1, LFA-1, Mac-1, and VLA-4 were located mainly at the boundary between liver parenchyma and the metastasis. At the ultrastructural level, ICAM-1-positive immune deposits were observed on the cellular membrane and in some transport vesicles of gastric metastatic cells. Further, the expression of all adhesion molecules was confirmed to sinusoidal endothelial cells and tumour vessels. It is concluded that the enhanced expression of adhesion molecules in liver sinusoids could be a marker for the assessment of the ability of sinusoidal endothelial cells to control the recruitment of leukocytes and monocytes to the metastatic site. They could also direct the adhesion of new circulating tumour cells to sinusoidal endothelium.
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PMID:Expression of cell adhesion molecules, their ligands and tumour necrosis factor alpha in the liver of patients with metastatic gastrointestinal carcinomas. 1236 2


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