bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2337: Effect of embryonic stem (ES) cell-conditioned microenvironment on the reprogramming of human cancer
Authors: Kim Myoung Ok , Cho Yong-Yeon , Kim Sung-Hyun , Jeong Chul-Ho , Lee Kun-Yeong , Jeon Young-Jin , Bode Ann M. , Dong Zigang 
Published: February 2011

Abstract
During embryonic development, the extracellular matrix (ECM) plays a critical role in the regulation of stem cells to different lineages, cell migration and proliferation. A recently developed 3-dimensional (3D) ES-conditioned matrigel matrix culture of metastatic melanoma cells induces reprogramming and differentiation. However, although the ES-cell conditioned microenvironment induces melanoma cell reprogramming to suppress invasive behavior, the mechanisms have not yet been clearly understood. To investigate the effect of the cancer cell microenvironment, we hypothesized that 1) the microenvironment might induce nuclear reprogramming; 2) microenvironment-induced reprogramming might affect cell proliferation; 3) microenvironment-induced reprogramming might induce differentiation-mediated cellular senescence; and 4) microenvironment-induced reprogramming causes a loss of anchorage-independent cell growth, which is a hallmark of cancer cell properties. Here, we found that the ES-conditioned 3D-microenvironment induced a dramatic change in the morphology of A431 human skin epidermoid carcinoma cells and SK-MEL-28 human skin malignant melanoma cells. In the anchorage-independent cell growth assay, we found that A431 and SK-MEL-28 cells grown in the 3D ES-conditioned microenvironment exhibited dramatically decreased colony growth in soft agar. Real time PCR analysis indicated that ES-conditioned microenvironment suppressed endogenous Oct4 and Nanog gene expression in A431 and SK-MEL-28 cells and inhibited c-jun and c-fos promoter activities, which are components of the AP-1 transcriptional factor complex. Very importantly, we found that the ES cell-conditioned microenvironment inhibited telomerase activity, resulting in the induction of cellular senescence in human skin melanoma cells. We found that ES-conditioned medium contained a greater amount of Gremlin, a natural inhibitor of TGF-β signaling. Gremlin treatment of A431 and SK-MEL-28 cells induced morphological changes as observed in the 3D ES-conditioned matrigel matrix. Our results demonstrated that the ES-cell conditioned microenvironment inhibited proliferation and induced cellular senescence of A431 and SK-Mel-28 cells through the inhibition of TGF-β signaling by Gremlin. Furthermore, our data strongly suggests that modulation of TGF-β signaling in the cancer microenvironment is a potential strategy to modulate cancer cell behaviors and properties.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2337.
Abstract 2338: Molecular mechanisms underlying cellular transformation by Tumor protein D52 overexpression
Authors: Della-Franca Austin , Catchpoole Daniel R. , Bright Robert K. , deFazio Anna , Byrne Jennifer A. 
Published: February 2011

Abstract
Background: Tumor protein D52 (D52) overexpression is characteristic of both adult and childhood cancers and has been associated with reduced overall survival in breast cancer patients and an increase in proliferation and metastatic capacity of transfected cell lines. However, little is known about the mechanism(s) by which D52 overexpression contributes to cellular transformation or tumour progression.
Aims: We aimed to identify genes which are differentially expressed in response to D52 expression in 3T3 fibroblasts, and to use these gene expression changes to predict cellular phenotypes which are altered by D52 expression.
Methods: Gene expression profiling was performed using Affymetrix expression microarray analysis. Up- and down-regulated gene lists were analysed using GOSTAT, Metacore and literature searches. Differential expression of candidate proteins were validated using Western blot analysis of intracellular protein extracts or precipitates from conditioned media. Migration and invasion assays were performed using Boyden chambers.
Results: D52 expression was associated with over 300 genes being differentially expressed at least two-fold relative to vector controls. A number of overexpressed genes were found to be normally involved in the inflammatory response. We focused on validating candidates such as COX-2, MMP-2 and Osteopontin as being overexpressed in D52-transfected cells relative to vector controls. We also confirmed an upregulation of phospho-AKT in D52 expressing cells, as reported by others. GOSTAT analysis revealed that gene ontology terms related to the extracellular matrix (ECM) were most over-represented amongst differentially expressed genes. The implied resultant ECM re-modelling was examined through migration and invasion assays, in which D52 expressing cells showed a significantly increased migratory and invasive capacity relative to vector control lines.
Conclusions: These results implicate D52 as a pro-inflammatory intermediate, whose expression may act to drive cancer progression via an increase in phospho-AKT, followed by the production of inflammatory molecules such as Osteopontin.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2338.
Abstract 234: Transcription factor LSF is a novel oncogene for hepatocellular carcinoma (HCC)
Authors: Yoo Byoung Kwon , Emdad Luni , Gredler Rachel , Chen Dong , Su Zhao-zhong , Fisher Paul B. , Sarkar Devanand 
Published: February 2011

Abstract
While the incidence of overall cancers is decreasing, Hepatocellular Carcinoma (HCC) is one of the few cancers the incidence of which is on an increase. The mortality rate of HCC parallels that of incidence since HCC is a highly aggressive cancer with extremely limited currently available therapeutic strategies. Understanding the molecular mechanism of hepatocarcinogenesis will help develop novel, targeted and more effective therapeutic regimen to counteract this fatal disease. Here, we demonstrate that the cellular transcriptional factor Late SV40 Factor (LSF) functions as an oncogene in HCC. The level of LSF expression is significantly increased in human HCC patients compared to matched non-neoplastic controls and normal liver and LSF expression significantly correlates with the stages and grades of HCC. Ectopic overexpression of LSF in nontumorigenic human HCC cells leads to highly aggressive, multi-organ metastatic tumors while inhibition of LSF in aggressive human HCC cells profoundly inhibits tumorigenic and metastatic properties in athymic nude mice. Affymetrix microarray studies identified novel LSF-downstream genes that are associated with cell growth, angiogenesis, invasion, metastasis, chemoresistance, and senescence. Osteopontin, a key molecule mediating tumor progression, especially metastasis, was identified as a downstream target gene of LSF. Promoter-reporter and chromatin immunoprecipitation analyses confirmed that LSF transcriptionally upregulates OPN by binding to its promoter. Knockdown of OPN gene in LSF-overexpressing HCC cells markedly inhibits LSF-mediated tumor progression including metastasis. This is the first report on the novel function of LSF as an oncogene in any cancer indication. Since LSF expression correlates with the advanced stages of the disease, it might be employed as a diagnostic/prognostic marker for HCC. The DNA binding domain of LSF might be targeted with small molecule inhibitors that might be developed as potential HCC therapeutic. Our findings thus have significant translational implications.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 234.
Abstract 2343: Overexpression of uPAR in the murine oral squamous cell carcinoma cell line AT84
Authors: Magnussen Synnøve , Haustreis Stine , Uhlin-Hansen Lars , Winberg Jan-Olof , Svineng Gunbjorg 
Published: February 2011

Abstract
Cancers of the oral cavity are associated with bad prognosis and have been so for the last 20-30 years. Almost half of the patients diagnosed with oral squamous cell carcinoma (SCC) will die from the disease. When comparing oral SCC to its counterpart in skin, one of the main features that differ between the two is the ability of the oral SCC to metastasize. A prerequisite for metastasis is the capability to invade the surrounding tissue and penetrate into the nearest blood- or lymphatic vessel. This initial step in metastasis requires several extracellular matrix degrading enzymes. One such enzyme is uPA (urokinase-type plasminogen activator), involved in pericellular proteolysis, where high levels are known to be correlated to bad prognosis in several cancers. Pro-uPA binds to its extracellularly located receptor uPAR. Upon binding, pro-uPA is cleaved and activated, and ample evidence shows that binding of uPA triggers uPAR-mediated cellular signalling. Being that uPAR has no membrane spanning domain, the signal transduction has to be mediated through one or several membrane partners. uPARs role in the regulation of cell adhesion, migration and proliferation have been dedicated to its interplay with membrane partners such as integrins, chemokine receptors, EGFR, G-protein coupled receptors and caveolin. To better understand the role of uPAR in the metastasis of oral SCCs, a mouse oral SCC cell line, AT84, was stably transfected with uPAR. AT84 was initially obtained from a spontaneously originating oral SCC of the C3H mouse (Lou et al., 2003; Schultz-Hector and Haghayegh, 1993). Characterization of these cell lines with respect to adhesion, migration, invasion, and effects on gene expression and activation of other proteolytic enzymes will be presented.
Lou, E., R.M. Kellman, R. Hutchison, and E.J. Shillitoe. 2003. Clinical and pathological features of the murine AT-84 orthotopic model of oral cancer. Oral Dis. 9:305-12.
Schultz-Hector, S., and S. Haghayegh. 1993. Beta-fibroblast growth factor expression in human and murine squamous cell carcinomas and its relationship to regional endothelial cell proliferation. Cancer Res. 53:1444-9.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2343.
Abstract 2344: Soluble MICA in cervical cancer is in a deglycosylated form: Implication for soluble MICA detection
Authors: Nanok C , Barusrux Sahapat , Leelayuwat C 
Published: February 2011

Abstract
Background: Major histocompatibility complex class I chain related A (MICA/PERB11.1) molecules are expressed as transmembrane proteins. They are ligands recognized by the natural killer cell receptor group (NKG)2D, an activating receptor on NK cells, gamma delta T cells and activated CD8 T cells. Up-regulated MICA expression was reported in many tumors. Shedding of MICA from tumor cells as soluble MICA (sMICA) is a mechanism for immune evasion. MICA proteins could be presented in various sizes from 43 to 75 kDa depending on degree of glycosylation. Eight potential N-glycosylation sites in a MICA molecule were reported. This study aimed to investigate the size of sMICA in sera of cervical cancer patients and women blood donors by western blot technique.
Methods: The sMICA*009 plasmid DNA was transfected to COS7 cells for recombinant sMICA protein production in culture supernatant. The recombinant sMICA protein was harvested and validated with mouse monoclonal anti-MICA antibody (WW6B7) by indirect ELISA and immunobloting. Molecular weight of deglycosylated recombinant sMICA protein treated with N-glycosidase F enzyme and sMICA in cervical cancer and healthy sera was determined.
Results: The recombinant sMICA and serum sMICA showed 62 kDa and 45 kDa in molecular weight, respectively. The molecular weight of recombinant sMICA treated with N-glycosidase F enzyme was reduced to 45 kDa which equal to serum sMICA indicating that sMICA in sera of patients and blood donor controls was in a deglycosylated form.
Conclusion: Recombinant sMICA produced in COS7 had a molecular weight of 62 kDa. In contrast, sMICA in sera was in a deglycosylated form and had a molecular weight of 45 kDa equal to in vitro deglycosylation with N-glycosidase F enzyme of produced recombinant sMICA. The mechanism and kinetic of deglycosylation of sMICA in sera await further investigation. It would be interesting to see whether this form of sMICA would affect sMICA detection in sera.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2344.
Abstract 2350: MicroRNA-145 suppresses cell invasion and metastasis by directly targeting mucin 1
Authors: Sachdeva Mohit , Mo Yin Yuan 
Published: February 2011

Abstract
MicroRNAs (miRNAs) are important gene regulators that could play a profound role in tumorigenesis. Our previous studies indicate that miR-145 is a tumor suppressor capable of inhibiting tumor cell growth both in vitro and in vivo. In this study, we show that miR-145 exerts its function in a cell-specific manner. Although miR-145 inhibits cell growth in MCF-7 and HCT-116 cells, it has no significant effect on cell growth in metastatic breast cancer cell lines. However, miR-145 significantly suppresses cell invasion in these cells, as shown by matrigel chamber assays; in contrast, the antisense oligo against miR-145 increases cell invasion. MiR-145 is also able to suppress lung metastasis in an experimental metastasis animal model. This miR-145-mediated suppression of cell invasion is in part due to the silencing of the metastasis gene mucin 1 (MUC1). Using luciferase reporters carrying the 3′-untranslated region of MUC1 combined with western blot and immunofluorescence staining, we identify MUC1 as a direct target of miR-145. Moreover, ectopic expression of MUC1 enhances cell invasion, which can be blocked by miR-145. Of interest, suppression of MUC1 by miR-145 causes a reduction of β-catenin as well as the oncogenic cadherin 11. Finally, suppression of MUC1 by RNAi mimics the miR-145 action in suppression of invasion, which is associated with downregulation of β-catenin and cadherin 11. Taken together, these results suggest that as a tumor suppressor, miR-145 inhibits not only tumor growth, but also cell invasion and metastasis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2350.
Abstract 2353: CREB regulates AP-2α transcription to determine the malignant phenotype of melanoma
Authors: Dobroff Andrey S. , Melnikova Vladislava O. , Villares Gabriel J. , Zigler Maya , Braeuer Russell R. , Wang Hua , Huang Li , Bar-Eli Menashe 
Published: February 2011

Abstract
The Activator protein-2 (AP-2) family of transcription factors consists of five different proteins which are involved in the regulation of cell proliferation, differentiation, apoptosis and carcinogenesis. Among these proteins, AP-2α has been suggested to function as a tumor suppressor in many cancers including melanoma. We have previously shown that in melanoma cell lines, acquisition of the metastatic phenotype is associated with loss of AP-2α expression and gain in expression of cAMP-responsive element (CRE)-binding protein (CREB). This inverse correlation is associated with increase of melanoma invasion and metastasis resulting in overexpression of the melanoma cell adhesion molecule MCAM/MUC18 and protease-activated receptor 1 (PAR-1). However, the molecular mechanism involved in AP-2α regulation during melanoma progression remains unknown. Analyses of AP-2α promoter for transcription factor binding sites showed two distinct CRE-like sites as well as four E2F1 sites. Herein, we propose that the inhibition of AP-2α during the transition from the Radial Growth Phase (RGP) to the Vertical Growth Phase (VGP) occurs at the transcriptional level and is regulated through binding of CREB and E2F1. Hence, AP-2α protein expression was found to be increased after utilizing small hairpin RNA (shRNA) targeting CREB in two human metastatic melanoma cell lines, A375SM and C8161. Interestingly, E2F1 expression level was found to be reduced by 50% after CREB silencing in both cell lines. We also found a 20-fold increase in the luciferase activity driven by the AP-2α promoter after silencing CREB in both cell lines. In addition, point mutations at CRE-like binding sites as well as E2F1 increased the AP-2α promoter activity by more then 5-fold. To further establish the involvement of E2F1 in AP-2α regulation, we transiently overexpressed E2F1 in a low-metastatic melanoma cell line, SB-2. The AP-2α protein level as well as the promoter activity was significantly inhibited as compared to control. Finally, using Chromatin Immunoprecipitation (ChIP) assays in both CREB silenced cell lines, we were able to confirm that CREB and E2F1 bind to the AP-2α promoter thereby inhibiting its expression. Taken together, our studies demonstrate that CREB regulates AP-2α expression, thus, contributing to the metastatic phenotype of melanoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2353.
Abstract 2356: The role of the Rac GTPases in PC-3 prostate cancer cell diapadesis
Authors: Pathak Surabhi , Chatterjee Moumita , Dubyk Cara W. , Sequeira Linda , van Golen Kenneth 
Published: February 2011

Abstract
The Rho GTPases are molecular switches intimately involved in cancer metastasis through orchestrating changes in the cytoskeleton leading to motility and invasion. Previously, we demonstrated that RhoC GTPase was sufficient and required for PC-3 prostate cancer invasion. Furthermore, we demonstrated that targeted down-regulation of RhoC using either a dominant-negative RhoC or by specific shRNAs led to increased and sustained activation of Rac1 GTPase. Increased levels of active Rac1 led to morphological, molecular and phenotypic changes reminiscent of epithelial to mesenchymal transition (EMT). Additionally, we demonstrated a requirement for active Rac1 GTPase in PC-3 tumor cell diapedesis across a bone marrow endothelial cell (BMEC) layer, an important step in prostate cancer skeletal metastasis. In the current study, we analyze the specific roles of Rac1, Rac3 and RhoG GTPases in tumor cell diapadesis. Use of specific siRNAs to down-regulate the individual Rac proteins demonstrated unique roles for each in promoting cell adhesion and diapedesis. We found Rac1 to be expressed at significantly higher levels than Rac3 or RhoG. However, RhoG appears to regulate PC-3 diapadesis at levels similar to Rac1. In contrast, Rac3 does not regulate diapadesis but controls PC-3 binding to substrates and BMECs. Together, these data suggest a role for coordinated activity of the Rac GTPases during diapadesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2356.
Abstract 2357: Defining the Ezrin-CLIC4 interaction in osteosarcoma
Authors: Mendoza Martin , Ren Ling , Davicioni Elai , Wai Daniel , Triche Timothy , Khanna Chand 
Published: February 2011

Abstract
Ezrin, a linker protein between the cytoskeleton and plasma membrane, plays an important role in the metastatic phenotype of cancers that includes osteosarcoma and rhabdomyosarcoma. To better understand the role of ezrin in metastasis, we have identified proteins that bind the N-terminus of ezrin using tandem mass spectrometry affinity chromatography. One of the mass spectrometry identified proteins is the p53, TNFα, and c-Myc regulated stress-response protein Chloride Intracellular Channel 4 (CLIC4). Under conditions of cell stress, CLIC4 has been shown to translocate to the nucleus and subsequently cause cell-cycle arrest and/or accelerate apoptosis in cancer cells including osteosarcoma. Emerging data from our lab suggests that ezrin may provide metastatic cells with an early survival advantage by helping to resist the stresses of metastasis and resultant apoptosis. Combining these two lines of reasoning, we hypothesized that ezrin prevents CLIC4 induced apoptosis during times of stress by maintaining CLIC4 out of the nucleus. Using cell free conditions we have demonstrated a direct relationship between ezrin and CLIC4 recombinant proteins and through co-immunoprecipitation in osteosarcoma cells. In addition, experiments to define the minimal binding determinants of the ezrin-CLIC4 interaction are currently underway. We have confirmed co-expression of ezrin and CLIC4 in multiple human osteosarcoma cell lines and human sarcomas using both immunohistochemistry and expression microarray. We have recently developed assays and reagents to monitor and manipulate CLIC4 nuclear localization under conditions of stress. The outcome of this work will be to define the nature and biological significance of the ezrin-CLIC4 interaction in metastasis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2357.