Home About us Contact
|
Home About us Contact | ||
|
|
||
Metastatic Ability (metastatic + ability)
Selected AbstractsThirty-kilodalton Tat-interacting protein suppresses tumor metastasis by inhibition of osteopontin transcription in human hepatocellular carcinoma,HEPATOLOGY, Issue 1 2008Jian Zhao It has been previously demonstrated that the 30-kDa Tat-interacting protein (TIP30) plays an important role in the suppression of hepatocarcinogenesis by acting as a tumor suppressor. Here we report that TIP30 suppresses metastasis of hepatocellular carcinoma (HCC) through inhibiting the transcription of osteopontin (OPN), a key molecule in the development of tumor metastasis. The expression of TIP30 messenger RNA was reverse to that of OPN messenger RNA in HCC cell lines. Ectopic expression of TIP30 greatly suppressed OPN expression, inhibited invasion of HCC cells through extracellular matrix (ECM) and adhesion with fibronectin in vitro, whereas down-regulation of TIP30 by RNA-mediated interference enhanced OPN expression and promoted metastatic abilities of HCC cells in vitro. Moreover, overexpression of TIP30 significantly inhibited the growth and lung metastases of HCC cells in nude mice. In contrast, down-regulation of TIP30 greatly promoted tumor cell growth and metastases in vivo. TIP30 repressed OPN transcription through interaction with Ets-1 and suppressed the transcriptional activity of Ets-1 and synergistic actions of Ets-1 and alkaline phosphatase-1. Thus, TIP30 may act as an Ets-1 modulator and inhibit tumor metastasis through abrogating Ets-1,dependent transcription. Moreover, expression of TIP30 was inversely associated with OPN expression in HCC tissue samples as detected by immunohistochemistry assay. Conclusion: Our results reveal a novel pathway by which OPN and possibly other Ets-1 target genes involved in tumor metastasis are regulated by TIP30 and elucidate a mechanism for metastasis promoted by TIP30 deficiency. (HEPATOLOGY 2008.) [source] KAI1 gene suppresses invasion and metastasis of hepatocellular carcinoma MHCC97-H cells in vitro and in animal modelsLIVER INTERNATIONAL, Issue 1 2008Jian-min Yang Abstract Background: Downregulation of KAI1 gene expression has been found in many types of cancer cells and is closely related to cancer invasion and metastasis. This study was aimed at investigating the effects and possible underlying mechanisms of KAI1 gene on invasion and metastasis of human hepatocellular carcinoma (HCC). Methods: The invasive ability, visco-elastic properties and cell adhesion forces were analysed in different HCC cells originating from the MHCC97-H cell line transfected with either the sense or the antisense KAI1 expression plasmid. Tumuorigenicity, metastatic abilities, extracellular matrix (ECM) and intercellular adhesion molecule-1 (ICAM-1) expression were also evaluated in the nude mouse models of the xenografted and orthotopic liver cancer cells. Results: Compared with their parental cells, in the HCC cells transfected with the sense KAI1 gene, the invasive ability in vitro was significantly decreased (P<0.01); the cellular elastic coefficients K1, K2 and , were significantly higher (P<0.05); the cells adhesion forces to fibronectin were significantly lower (P<0.01). The sense KAI1 gene transfection into the cancer cells also inhibited their invasion and lung metastasis in the orthotopic liver cancer nude mice. However, the opposite changes were observed in the HCC cells transfected with the antisense KAI1 gene. KAI1 gene transfection also affected ECM and ICAM-1 expression in the transplanted liver cancer. Conclusion: The KAI1 gene plays an important role in the invasion and metastasis of human HCC and its upregulation in HCC cells suppresses their invasive and metastatic abilities. KAI1 gene functioned as a metastasis inhibitor by regulating the HCC cell biophysical behaviours including aggregation, adhesion, motility and visco-elastic properties. [source] CD44 isoform expression in synovial sarcoma correlates with epitheliogenesis but not prognosisHISTOPATHOLOGY, Issue 2 2000R J Sneath Aims : We immunohistochemically determined the expression of CD44 standard and splice variant isoforms in a series of synovial sarcomas and sought correlations with histological subtype and clinical parameters including outcome. Methods, and results: From 39 patients, a total of 56 formalin-fixed and paraffin-embedded tumour samples (including initial, recurrent and metastatic tumours) were used to immunohistochemically evaluate the expression of epitopes encoded by CD44s and the CD44 splice variants CD44v3,v10. Significance of proposed prognostic indicators was evaluated in relation to the survival, time to local recurrence and time to metastases using log-rank analysis. Sixty-four percent of synovial sarcomas expressed CD44s and 46% expressed CD44v3,v10 (var). Synovial sarcomas with epithelial or epithelioid areas preferentially expressed CD44s in these areas when compared with the spindle cell element. There were no correlations with clinical parameters or outcome. Conclusions: The expression of CD44 was not found to correlate with survival, local recurrence or metastatic ability. In synovial sarcoma, CD44 and variant isoform expression appears to be associated with the degree of epithelial differentiation. CD44 expression in synovial sarcoma shows interesting similarities to CD44 expression in embryological epitheliogenesis. [source] High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic abilityJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009Alysha K. Croker Abstract Cancer stem cells (CSCs) have recently been identified in leukaemia and solid tumours; however, the role of CSCs in metastasis remains poorly understood. This dearth of knowledge about CSCs and metastasis is due largely to technical challenges associated with the use of primary human cancer cells in pre-clinical models of metastasis. Therefore, the objective of this study was to develop suitable pre-clinical model systems for studying stem-like cells in breast cancer metastasis, and to test the hypothesis that stem-like cells play a key role in metastatic behaviour. We assessed four different human breast cancer cell lines (MDA-MB-435, MDA-MB-231, MDA-MB-468, MCF-7) for expression of prospective CSC markers CD44/CD24 and CD133, and for functional activity of aldehyde dehydrogenase (ALDH), an enzyme involved in stem cell self-protection. We then used fluorescence-activated cell sorting and functional assays to characterize differences in malignant/metastatic behaviour in vitro (proliferation, colony-forming ability, adhesion, migration, invasion) and in vivo (tumorigenicity and metastasis). Sub-populations of cells demonstrating stem-cell-like characteristics (high expression of CSC markers and/or high ALDH) were identified in all cell lines except MCF-7. When isolated and compared to ALDHlowCD44low/, cells, ALDHhiCD44+CD24, (MDA-MB-231) and ALDHhiCD44+CD133+ (MDA-MB-468) cells demonstrated increased growth (P < 0.05), colony formation (P < 0.05), adhesion (P < 0.001), migration (P < 0.001) and invasion (P < 0.001). Furthermore, following tail vein or mammary fat pad injection of NOD/SCID/IL2, receptor null mice, ALDHhiCD44+CD24, and ALDHhiCD44+CD133+ cells showed enhanced tumorigenicity and metastasis relative to ALDHlowCD44low/, cells (P < 0.05). These novel results suggest that stem-like ALDHhiCD44+CD24, and ALDHhiCD44+CD133+ cells may be important mediators of breast cancer metastasis. [source] Current and emerging concepts in tumour metastasis,THE JOURNAL OF PATHOLOGY, Issue 1 2010Caroline Coghlin Abstract Disseminated cancer accounts for most deaths due to malignancy. Despite this, research has focused predominantly on tumour development and progression at the primary site. Recently, attention has shifted towards the field of tumour metastasis. Several new and exciting concepts that have emerged in the past few years may shed light on this complex area. The established canonical theory of tumour metastasis, as a process emerging from a stepwise accumulation of genetic events fuelled by clonal evolution, has been challenged. New evidence suggests that malignant cells can disseminate at a much earlier stage than previously recognized in tumourigenesis. These findings have direct relevance to clinical practice and shed new light on tumour biology. Gene-profiling studies support this theory, suggesting that metastatic ability may be an innate property shared by the bulk of cells present early in a developing tumour mass. There is a growing recognition of the importance of host factors outside the primary site in the development of metastatic disease. The role of the ,pre-metastatic niche' is being defined and with this comes a new understanding of the function of bone marrow-derived progenitor cells in directing the dissemination of malignant cells to distant sites. Current research has highlighted the crucial roles played by non-neoplastic host cells within the tumour microenvironment in regulating metastasis. These new concepts have wide-ranging implications for our overall understanding of tumour metastasis and for the development of cancer therapeutics. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] 2-Chloroadenosine modulates PAR-1 and IL-23 expression and enhances docetaxel effects on PC3 cellsTHE PROSTATE, Issue 4 2008Alba Minelli Abstract BACKGROUND Docetaxel-based chemotherapy is the only treatment that demonstrated an overall survival benefit in men with hormone refractory prostate cancer. 2-CADO inhibits the growth of PC3 cells by inducing apoptosis and cell cycle arrest through a mechanism that involves cellular uptake. METHODS Androgen-independent and -sensitive (PC3 and LNCaP) prostate cancer cells and non-neoplastic HECV cells were used in the study. Proliferation and cell cycle progression were analyzed in the presence of 2-CADO and Docetaxel. Invasive potential was assessed by soft agar assay and metastatic ability by adhesion assay. IL-23 and PAR-1 expression were determined by real time PCR. RESULTS 2-CADO pre-treatment followed by Docetaxel at subclinical dosage reduced the viability of either PC3 or LNCaP while it did not enhance Docetaxel-induced cytotoxicity in adherent non-neoplastic HECV. The drugs reduced the invasive potential of PC3 cells by inducing apoptosis and blocking cell cycle progression in the S-phase. Down-regulation of PAR-1 gene expression resulted in a slightly lower metastatic potential, whereas up-regulation of IL-23 induced the activation of the immune system. CONCLUSIONS Pretreatment of PC3 cells with 2-CADO decreased the effective concentration of Docetaxel, lowered the metastatic potential, and induced the production of cytokines known to stimulate the immune response against cancer. The treatment was effective for prostate cancer cells independently on their androgen sensitiveness. Prostate 68: 360,372, 2008. © 2008 Wiley-Liss, Inc. [source] Patterns of spread in an orthotopic mouse model of bladder cancerBJU INTERNATIONAL, Issue 2006J.P. BRENNAN Purpose:, To develop an orthotopic model of muscle-invasive transitional cell carcinoma (TCC) of the bladder which models primary tumour growth and metastasis. Methodology:, Cell lines were derived from the TCC cell line T24 (Tsu-Pr1) using in vivo selection for metastatic ability (Chaffer et al. Clin Exp Metastasis 2005; 22(2): 115,25). Each of these cell lines (Tsu-Pr1 and sub-lines, B1 and B2) was then injected intramurally into the mouse bladder wall (n = 25 × 3). The cell lines were also injected intravesically and intraperitoneally (n = 15 × 3 in each group). Results:, There were no differences between the three sub-lines in primary tumour formation, presence of macroscopic metastases and survival. This model produced more macroscopic and lymph node metastases in comparison with other orthotopic models reported in the literature. After intraperitoneal injection, the B2 cell line produced a higher number of discrete intra-abdominal masses in comparison with the parental line. This is likely to be related to the phenotype of the cells with parental cells being more mesenchymal, versus the B2 sub-line, which has more epithelial characteristics. Conclusion:, The TSU-Pr1 series is a useful, clinically relevant model of muscle-invasive TCC. In addition, this model may also provide insights into the role of mesenchymal-epithelial transition in the metastatic process. [source] | ||||||||||||||||||||||