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)

Adenoid cystic carcinoma (ACC) is a generally slow-growing but highly malignant salivary gland neoplasm with remarkable capacities for local invasion and lung metastasis. The precise characteristics of ACC are not fully understood because there was no suitable animal model. We have successfully established a new human tumor line (ACCI) derived from ACC of the oral floor, which showed a cribriform pattern histologically and serially transplantable into nude mice. This tumor developed spontaneous metastasis to the neck at the second passage level, and the histological feature changed from ACC to undifferentiated carcinoma (ACCIM). ACCIM caused spontaneous metastasis to the lung at high incidence when transplanted subcutaneously in nude mice. In this study, we examined the characteristics of this interesting human ACC metastatic line. Tumor fragments were subcutaneously transplanted into nude mice and tumor growth was measured at 1-week intervals. Histological and immunohistochemical examinations were performed. As a result, the tumor growth rate of ACCIM increased as compared to that of ACCI, and the PCNA labeling index was elevated. Furthermore, ACCIM produced multiple metastases to lymph nodes and lungs 5 months after transplantation, and all mice died within 6 months. These multiple metastases were also confirmed in orthotopic transplantation to the tongue. RT-PCR analysis revealed that ACCIM expressed human beta-actin, indicating its human origin. From these findings, ACCIM transplanted into nude mice would provide a useful model for investigating the biological behaviour of ACC.
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PMID:Establishment of nude mouse transplantable model of a human adenoid cystic carcinoma of the oral floor showing metastasis to the lymph node and lung. 1714 80

Ezrin primarily acts as a linker between the plasma membrane and the cytoskeleton and is a key component in tumor metastasis. In the present study, RNA interference (RNAi) using ezrin small hairpin RNAs (ezrin shRNAs) was used to define the roles of ezrin in the regulation of malignant behaviors of human breast cancer. The highly metastatic human breast cancer cell MDA-MB-231, in which ezrin mRNA and protein levels are the highest, was selected as a cell model in vitro. In addition, we also found that ezrin expression was up-regulated and its immuno-staining trans-located from cell membrane to cytoplasm, whereas E-cadherin expression decreased and showed the same cell distribution as ezrin in lymphatic metastases of human breast carcinomas. After repression of ezrin by more than 85% of G3PDH and 75% of beta-actin in mRNA and protein levels was maintained in the stable expressing ezrin shRNAs MDA-MB-231 cell clones, the abilities of cell motility and invasiveness were obviously inhibited with a 4-fold and 2-fold, respectively, and the altered cell polarity was observed. Western blot analyses further revealed that the silencing of ezrin induced an increased E-cadherin expression and a decreased phosphorylation of beta-catenin by inhibiting phosphorylation levels of c-src. These data indicate that ezrin overexpression positively correlated with metastatic potentials of human breast cancer cells, especially lymphatic system metastasis. Decreased ezrin expression by shRNA reversed metastatic behaviors of human breast cancer cells by inducing c-src-mediated E-cadherin expression, suggesting that ezrin may have potential values in assessing lymphatic metastasis of human breast cancers.
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PMID:Ezrin silencing by small hairpin RNA reverses metastatic behaviors of human breast cancer cells. 1815 31

VICKZ proteins are a highly conserved family of RNA binding proteins, implicated in RNA regulatory processes such as intracellular RNA localization, RNA stability, and translational control. During embryogenesis, VICKZ proteins are required for neural crest migration and in adults, the proteins are overexpressed primarily in different cancers. We hypothesized that VICKZ proteins may play a role in cancer cell migration. In patients, VICKZ expression varies with tumour type, with over 60% of colon, lung, and ovarian tumours showing strong expression. In colorectal carcinomas (CRCs), expression is detected at early stages, and the frequency and intensity of staining increase with progression of the disease to lymph node metastases, of which 97% express the protein at high levels. Indeed, in stage II CRC, the level of VICKZ expression in the primary lesion correlates with the degree of lymph node metastasis. In culture, VICKZ proteins rapidly accumulate in processes at the leading edge of PMA-stimulated SW480 CRC cells, where they co-localize with beta-actin mRNA. Two distinct cocktails of shRNAs, each targeting all three VICKZ paralogues, cause a dramatic drop in lamellipodia and ruffle formation in stimulated cells. Thus, VICKZ proteins help to facilitate the dynamic cell surface morphology required for cell motility. We propose that these proteins play an important role in CRC metastasis by shuttling requisite RNAs to the lamellipodia of migrating cells.
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PMID:A role for VICKZ proteins in the progression of colorectal carcinomas: regulating lamellipodia formation. 1853 85

The hTERT gene encodes the telomerase catalytic subunit that plays a key role in cancer cell immortalization. Earlier, hTERT amplification was detected in squamous cell cervical carcinomas (SCC), however possible relations between elevated hTERT mRNA level and gene amplification was not studied. Here, we compared the hTERT expression and copy number in the same tumors by quantitative real-time PCR. The hTERT DNA copy number was virtually unchanged in all 33 studied tumors, when compared to normal tissues. This result was confirmed using two reference genes beta-actin and beta-D-glucuronidase. Nevertheless, the activation of hTERT expression was found in 80% of cases (37/46, p<0.001). There was no correlation between the degree of mRNA increase and the tumor size and/or presence of metastases. No hTERT gene expression was observed in 20% of cases (9/46), while the control GADPH expression was unchanged. The detected elevation of the hTERT mRNA level was found using primers specific to functionally active full-length isoform of mRNA. Similar results were obtained with SCC cell lines carrying human papilloma virus (HPV) genomes. We conclude that frequent activation of hTERT expression in SCC is not associated with gene amplification.
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PMID:Activation of the hTERT expression in squamous cell cervical carcinoma is not associated with gene amplification. 1863 13

Pim kinases are emerging as important mediators of cytokine signalling pathways in hematopoietic cells, and contribute to the progression of certain leukemias and solid tumors. The mRNA expression of pim-1, a putative oncogenic serine-threonine kinase, was determined in non-small cell lung cancer (NSCLC) patients. Sixty-eight patients with potentially curative resections (R0 resections) for NSCLC in histopathological stages I-IIIA were included. An analysis of pim-1 mRNA expression was performed on paired tumor and normal lung tissue samples by quantitative real-time reverse transcriptase-PCR (RT-PCR) standardized for beta-actin. Pim-1 expression in the tumor (median 0.28) was significantly down-regulated (p<0.0001) compared to the paired normal tissue (median 4.96). Immunohistochemistry showed a strong expression of Pim-1 protein in the normal respiratory epithelium and a lower expression in the tumor cells. A significant association between the pim-1 down-regulation and occurrence of lymph node metastases (p=0.05) was detected. The down-regulation of pim-1 mRNA was demonstrated for 59 out of 68 lung cancer patients (86.8%). Down-regulation occurs already in the early stage of NSCLC and is either directly involved in the lymphatic progression in NSCLC or represents a surrogate marker.
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PMID:Frequent down-regulation of pim-1 mRNA expression in non-small cell lung cancer is associated with lymph node metastases. 1869 14

Rhabdomyosarcoma (RMS) are soft-tissue sarcoma commonly encountered in childhood. RMS cells can acquire invasive behavior and form metastases. The metastatic dissemination implicates many proteases among which are mu-calpain and m-calpain. Study of calpain expression and activity underline the deregulation of calpain activity in RMS. Analysis of kinetic characteristics of RMS cells, compared to human myoblasts LHCN-M2 cells, shows an important migration velocity in RMS cells. One of the major results of this study is the positive linear correlation between calpain activity and migration velocity presenting calpains as a marker of tumor aggressiveness. The RMS cytoskeleton is disorganized. Specifying the role of mu- and m-calpain using antisense oligonucleotides led to show that both calpains up-regulate alpha- and beta-actin in ARMS cells. Moreover, the invasive behavior of these cells is higher than that of LHCN-M2 cells. However, it is similar to that of non-treated LHCN-M2 cells, when calpains are inhibited. In summary, calpains may be involved in the anarchic adhesion, migration and invasion of RMS. The direct relationship between calpain activity and migration velocities or invasive behavior indicates that calpains could be considered as markers of tumor aggressiveness and as potential targets for limiting development of RMS tumor as well as their metastatic behavior.
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PMID:Calpains: markers of tumor aggressiveness? 2019 80


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