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)

Expression of activated leukocyte cell adhesion molecule (ALCAM)/CD166 correlates with the aggregation and metastatic capacity of human melanoma cell lines (Am J Pathol 1998, 152:805-813). Immunohistochemistry on a series of human melanocytic lesions reveals that ALCAM expression correlates with melanoma progression. Most nevi (34/38) and all thin melanomas studied (Clark levels I and II) did not express ALCAM. In contrast, immunoreactivity was detected in the invasive, vertical growth phase of 2 of the 13 Clark level III lesions tested. The fraction of positive lesions further increased in Clark level IV (13/19) and in Clark level V (4/4) lesions. ALCAM expression was exclusively detectable in the vertical growth phase of the primary tumor. In melanoma metastases, approximately half of the lesions tested (13/28) were ALCAM positive. According to the Breslow-thickness, ALCAM expression was observed in less than 10% of the lesions that were thinner than 1.5 mm and in over 70% of the lesions that were thicker than 1.5 mm. Our results strongly suggest that ALCAM plays an important role in melanocytic tumor progression and depict it as a new molecular marker for neoplastic progression of primary human melanoma.
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PMID:Activated leukocyte cell adhesion molecule/CD166, a marker of tumor progression in primary malignant melanoma of the skin. 1070 91

Metastasis frequently occurs during and/or after chemotherapy resulting in failure. This suggests that inadequate chemotherapy promotes the emergence of more malignant tumor cells with metastatic potential. However, it is not determined how chemotherapy could promote the metastatic progression of tumor cells. In this study, we isolated highly metastatic clones from the tumors treated with ADR using an in vivo experimental model, in which non-metastatic tumor cells were inoculated s.c. in mice, treated with or without Adriamycin and then culture lines were re-established from the tumors. Then we isolated cDNAs for activated leukocyte cell adhesion molecule (ALCAM), osteopontin, and annexin II as candidates for metastasis-promoting genes with the use of a PCR-based subtraction method. Further we examined the metastatic potential of transfectants over-expressing ALCAM, osteopontin, or annexin II and combinations of them. Metastasis to the lung was observed in the mice where transfectants over-expressing ALCAM plus annexin II had been inoculated via tail vein. These results suggest that the over-expression of ALCAM and annexin II play a role in the metastatic progression after chemotherapy with ADR.
Clin Exp Metastasis 2000
PMID:Activated leukocyte cell adhesion molecule (ALCAM) and annexin II are involved in the metastatic progression of tumor cells after chemotherapy with Adriamycin. 1120 37

Cluster designation (CD) antigens are cell surface markers that can be used to identify constituent cell populations of an organ. We have previously determined the CD phenotype of normal prostate parenchymal cells and are now extending this analysis to prostate cancer. Since expression of CD antigens is associated with cellular differentiation, cancer cells may differ from their normal counterpart in their CD profile. Compared with luminal secretory cells, prostate adenocarcinoma cells are frequently negative for CD10 and CD13, express increased levels of the cell activation molecule CD24, and decreased levels of the apoptosis-associated multifunctional enzyme CD38. Expression of CD57, CD63, CD75s, CD107a, CD107b, CD164, and CD166 by cancer cells is similar to that of secretory cells. Prostate basal epithelial cells do not express the CD antigens characteristic of prostate secretory cells; and the basal cell CD markers, CD29, CD44, CD49b, CD49f, CD104, and nerve growth factor receptor (NGFR) are not expressed by cancer cells. The preferential expression of secretory cell-associated CD markers by prostate cancer cells suggests a closer lineage relationship between cancer cells and secretory cells than basal cells. Although the above cancer CD phenotype was the most frequently seen, some prostate cancers contained populations of CD10- and/or CD13-positive cells, and CD57-negative cells. Furthermore, the cancer phenotype of tumor metastasis is different. Despite its low frequency in primary tumors, CD10 is expressed by virtually all of the nodal metastases of prostate cancer. In addition, stromal fibromuscular cells associated with primary prostate cancer differ from stromal cells in benign prostate tissue by an increased level of expression of the cell activation molecule, CD90. In summary, our data show that the CD marker expression profile of prostate cancer cells most closely resembles that of secretory prostate epithelial cells and that some prostate cancers consist of heterogeneous cell populations as distinguished by CD-marker expression profiles.
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PMID:Heterogeneity in primary and metastatic prostate cancer as defined by cell surface CD profile. 1550 25

Orchestrated modulation of cell adhesion is essential for development and homeostasis in multicellular organisms. It optimizes embedding of the cell in its dynamic environment and facilitates appropriate cell responses and intercellular communication. Chronic disturbance of this delicate equilibrium causes defects in tissue architecture and sometimes cancer. In tumor cell biology, dynamic control of adhesion molecules is important to proceed through the metastatic cascade and to allow cell release from the primary tumor, invasion of the surrounding matrix, intravasation and adhesion to vascular endothelial cells to facilitate extravasation. Intertwined and multiple adhesive interactions rather than individual interactions presumably play critical roles in neoplastic development. Yet, knowledge of the contribution of each individual adhesion molecule is essential to unravel this network of interactions. This review will focus on activated leukocyte cell adhesion molecule (ALCAM/CD166) and its role in human melanoma progression. It is hypothesized that ALCAM may function as a cell surface sensor to register local growth saturation and to regulate cellular signaling and dynamic responses.
Cancer Metastasis Rev 2005 Jun
PMID:Activated leukocyte cell adhesion molecule (ALCAM/CD166): signaling at the divide of melanoma cell clustering and cell migration? 1598 33

We have investigated the frequency of methylation of several tumour suppressor genes in uveal melanoma. As the loss of one copy of chromosome 3 (monosomy 3), which is found in about half of these tumours, is tightly associated with metastatic disease, a special emphasis was laid on genes located on this chromosome, including the fragile histidine triad (FHIT), von Hippel-Lindau (VHL), beta-catenin (CTNNB1), activated leukocyte cell adhesion molecule (ALCAM) and retinoic acid receptor-beta2 (RARB) genes. In addition, the methylation patterns of the CpG-rich regions 5' of the E-cadherin (CDH1), p16/cyclin-dependent kinase inhibitor 2 A (CDKN2A) and retinoblastoma (RB1) genes were analysed by bisulphite genomic sequencing or methylation-specific PCR (MSP). Furthermore, the SNRPN and D15S63 loci, which are located in the imprinted region of chromosome 15, were included in the study. Aberrant methylation was detected in nine of 40 tumours analysed: The imprinted SNRPN and D15S63 loci were hypermethylated in three tumours, all of which retained both copies of chromosome 3. Methylated RARB alleles were detected in three tumours, whereas in three other tumours CDKN2A was found to be methylated. As we did not find RARB and CDKN2A preferentially methylated in tumours with monosomy 3, which is a significant predictor of metastatic disease, we suggest that these genes may play a causative role in the formation of uveal melanoma but not in the development of metastases.
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PMID:Methylation analysis of several tumour suppressor genes shows a low frequency of methylation of CDKN2A and RARB in uveal melanomas. 1862 84

A loss of human leukocyte antigen (HLA) expression in clinical tumors is one of their escape mechanisms from immune attack by HLA-restricted effector cells. In this study, the induction of HLA-unrestricted effector cells, gamma delta T cells, using zoledronate (ZOL) and interleukin (IL)-2 in vitro was investigated in patients with metastatic cancer. Peripheral blood mononuclear cells (PBMCs) from 10 cancer patients (8 colorectal and 2 esophageal) with multiple metastases and ascites lymphocytes from 3 cancer patients (1 gastric and 2 colorectal) were stimulated with varied concentrations of ZOL plus 100 U/ml IL-2 for 48 hr followed by culturing with IL-2 alone for 12 days. Lymphocyte proliferative responses were determined using 3H-TdR uptakes and interferon (IFN)-gamma production was evaluated using enzyme-linked immunosorbent assay. Surface phenotyping was performed using flow cytometry. Cytotoxic activity of effector cells was determined using 51Cr-releasing assay. It was found that proliferative responses of PBMCs were significantly stimulated with ZOL plus IL-2 when compared with IL-2 alone, showing 200 to 500-fold expansions for 2 weeks, although ZOL alone induced no response. The optimal concentration of ZOL was 1-5 microM. Ascites lymphocytes could also be stimulated with ZOL plus IL-2. The proliferative responses were remarkable in patients whose PBMCs could produce high levels of IFN-gamma during an initial 48-hr stimulation using ZOL plus IL-2. Removal of an adherent cell fraction before the induction augmented the proliferative responses in patients who otherwise had low-grade proliferative responses. Generated cells comprising approximately 90 or 20% in PBMCs from healthy donors or cancer patients, respectively, expressed gamma delta-type T-cell receptor. Gamma delta T cells showed high cytotoxic activity against CD166-positive TE12 and TE13 cancer cells but not against CD166-negative MKN45 cells. The cytotoxic activity against TE13 cells was augmented when target cells were pre-treated overnight with ZOL. These results suggest that ZOL in the presence of IL-2 can efficiently stimulate the proliferation of gamma delta T cells, which have cytotoxic properties against cancer cells. The use of zoledronate-activated killer (ZAK) cells should be encouraged in possible adoptive immunotherapy trials for patients with incurable cancer.
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PMID:Induction of gamma delta T cells using zoledronate plus interleukin-2 in patients with metastatic cancer. 1940 May 55

Fumagillin is an inhibitor of type 2 methionine aminopeptidase that can block blood vessel formation, but its molecular mechanism and therapeutic value in colon cancer still remain to be elucidated. In this study, male severe combined immunodeficiency (SCID) mice were injected with colon cancer cells in the subcutis and then treated with Fumagillin and Cyclo (Arg-Gly-Asp-D-Phe-Val), an integrin alphavbeta(3) antagonist. The tumor weight, microvessel density (MVD), and number of pulmonary metastatic foci were examined. Gene expression profiles were examined by microarray analysis of human umbilical endothelial cells (HUVEC). The Fumagillin-treated mice had smaller tumor mass, fewer pulmonary metastases, and lower MVD-CD105 levels than control animals. In vitro proliferation and tube formation of HUVEC was also significantly decreased by Fumagillin. Microarray analysis of Fumagillin-treated HUVEC showed upregulation of 71 genes and downregulation of 143 genes. Expression changes were involved in cell proliferation, migration, adhesion, and gene transcription. Quantitative real-time-polymerase chain reaction and western blotting showed decreased expression of cyclin E2, activated leukocyte cell adhesion molecule (ALCAM), and intercellular adhesion molecule-1 (ICAM-1) genes in the presence of Fumagillin. This downregulation by Fumagillin may be involved in the anti-angiogenesis by Fumagillin. In conclusion, Fumagillin was found to suppress colorectal cancer growth and metastasis by suppressing angiogenesis.
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PMID:Fumagillin inhibits colorectal cancer growth and metastasis in mice: in vivo and in vitro study of anti-angiogenesis. 1956 8

With metastatic disease at diagnosis for 70% of patients, ovarian cancer represents the most lethal gynecological malignancy. Ovarian carcinomas are aggressive malignancies that can evade immune surveillance and frequently develop into metastases. The tumor microenvironment is decisive for preventing immune attack but, in the case of ovarian carcinoma, the mechanisms are unclear. We recently isolated a novel type of stromal cell from the ascitis of patients with ovarian carcinoma that interacts with epithelial ovarian cancers conferring them chemoresistance. These cells, called Hospicells, have the cell surface markers CD9, CD10, CD29, CD146 and CD166. Here, we investigated whether Hospicells also have immunomodulatory functions that might interfere with immunity to cancer. We report that Hospicells inhibit the proliferation of human CD4(+), CD8(+) and Vgamma9Vdelta2 T cells in vitro and the production of cytokines by these immune cells. The immunosuppression of CD4(+) T cells is independent of direct contact with the Hospicells and is mainly due to nitric oxide produced by the inducible nitric oxide synthase and to products of the tryptophan degradation by indoleamine 2,3-dioxygenase. We proposed that Hospicells in the microenvironment of the tumor mediate immunosuppression of T cells and thus allow ovarian cancers to evade immune surveillance. Targeting of Hospicells could be an alternative to strong chemotherapy through the recovery of immune responses against tumor cells.
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PMID:Hospicells derived from ovarian cancer stroma inhibit T-cell immune responses. 1973 80

The expression of the activated leukocyte cell adhesion molecule (ALCAM and CD166) is increased in various types of cancer. We aimed to evaluate its role as a prognostic marker for esophageal cancer (EC). We retrospectively analyzed ALCAM expression in 299 primary lesions, 147 lymph node and 46 distant metastases from EC patients, on a tissue microarray using immunohistochemistry. Bone marrow samples from representative cancer patients (n = 16), taken before primary surgery, were stained by double-immunofluorescence for ALCAM and cytokeratins (CK). Blood serum samples from 236 cancer patients and 127 controls were analyzed for serum ALCAM (s-ALCAM) by ELISA. The immunohistochemical analysis showed increased ALCAM expression in the majority of lesions (primary tumor 71%, lymph node 76% and distant metastases 80%). ALCAM expression was not associated with histopathological parameters except for tumor grading (p = 0.015). ALCAM-positive patients had significantly worse recurrence-free and overall survival (OS; p = 0.002). Disseminated tumor cells (DTC) in bone marrow showed two phenotypes, ALCAM+/CK+ (36%) and ALCAM-/CK+ (64%). Multivariate analysis revealed that ALCAM expression and elevated s-ALCAM serum values are powerful prognostic variables for OS in patients with EC (hazard ratio [HR] 3.987, 95% confidence interval [95%CI] 1.906-8.340, p < 0.001 and HR 1.915, 95%CI 1.021-3.592, p = 0.043). The results of our study provide preliminary evidence for the potential clinical utility of ALCAM as a prognostic biomarker for EC, which might be a basis for future clinical application. In addition, ALCAM expression in a subset of DTC of the bone marrow indicates a potential function in the metastatic cascade of EC.
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PMID:ALCAM (CD166) expression and serum levels are markers for poor survival of esophageal cancer patients. 2185 15

Metastasis is a major clinical problem and results in a poor prognosis for most cancers. The metastatic pathway describes the process by which cancer cells give rise to a metastatic lesion in a new tissue or organ. It consists of interconnecting steps all of which must be successfully completed to result in a metastasis. Cell-cell adhesion is a key aspect of many of these steps. Adhesion molecules belonging to the immunoglobulin superfamily (Ig-SF) commonly play a central role in cell-cell adhesion, and a number of these molecules have been associated with cancer progression and a metastatic phenotype. Surprisingly, the contribution of Ig-SF members to metastasis has not received the attention afforded other cell adhesion molecules (CAMs) such as the integrins. Here we examine the steps in the metastatic pathway focusing on how the Ig-SF members, melanoma cell adhesion molecule (MCAM), L1CAM, neural CAM (NCAM), leukocyte CAM (ALCAM), intercellular CAM-1 (ICAM-1) and platelet endothelial CAM-1 (PECAM-1) could play a role. Although much remains to be understood, this review aims to raise the profile of Ig-SF members in metastasis formation and prompt further research that could lead to useful clinical outcomes.
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PMID:The role of immunoglobulin superfamily cell adhesion molecules in cancer metastasis. 2227 1


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