bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1435: Analyzing the role of CXCR and IGF-IR in modulating actin dynamics in neuroblastoma cells
Authors: Muller James , Sabanayagam Chandran , van Golen Cynthia M. 
Published: June 2012

Abstract
The sensory cues that developing neurons use to control the pattering of neurite outgrowth are currently not well defined. CXCR4 and the insulin like growth factor receptor (IGF1r) have been implicated in the regulation of chemotaxis, neuronal migration, and axonal guidance. In addition to these chemokine receptors role in the guidance of neuronal development, an increasing body of evidence shows they are up-regulated in many late stage and metastatic cancers. Neuroblastoma, a cancer of neural crest origin, often expresses high levels of CXCR4 and IGF1r, and depending upon the level of differentiation, is capable of producing fully extended axons. The mediator of the cytoskeletal changes seen in axonal extension is primarily carried out by actin polymerization. In order to better understand the role of CXCR4 and IGF1r role in mediating these cytoskeletal changes we used western blots and immunocytochemistry / confocal microscopy to analyze the neuroblastoma cell line SHSY-5Y. We were able to show that indeed both receptors are involved in neuronal outgrowth. However, the individual effects of treatment with the receptors ligand resulted in different cellular morphologies. CXCR4 stimulation resulted in a more differentiated neuronal form, while IGF1r stimulation resulted in a very immature neuronal morphology with shorter broader processes. Finally, we were able to quantitate the effects of treatment to a wide array of phenotypic patterns that shows the connection between our observed morphological changes to show that these observations are real effects of treatment.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1435. doi:10.1158/1538-7445.AM2011-1435
Abstract 1440: Downregulation of Pdcd4 leads to epithelial to mesenchymal transition and promotes metastasis in nude mice
Authors: Wang Qing , Zhang Yong , Yang Hsin-Sheng 
Published: June 2012

Abstract
Progression of benign tumor into invasive carcinoma is a major cause of death in cancer patients. Programmed cell death 4 (Pdcd4) is a novel tumor suppressor, which inhibits TPA-induced transformation and tumor phenotype in mouse epidermal JB6 cells. It has been reported that overexpression of pdcd4 cDNA significantly reduces invasive ability of colon carcinoma and breast carcinoma cells in Matrigel invasion assays. Conversely, knockdown of Pdcd4 leads to fibroblast-like transition, promotion of Matrigel invasion, and activation of β-catenin dependent transcription. Activation of β-catenin dependent transcription by Pdcd4 knockdown results in up-regulation of urokinase-type plasminogen activator receptor (u-PAR) and c-Myc expression. Knockdown of u-PAR or c-Myc inhibits invasion in Pdcd4 knockdown cells, suggesting that both u-PAR and c-Myc contribute to the enhanced invasion induced by Pdcd4 knockdown. However, it is unclear whether down-regulation of Pdcd4 promotes metastasis in vivo.
In this study, we demonstrated that knockdown of Pdcd4 decreases the expression of epithelial markers (α-catenin and γ-catenin) and increases the protein level of mesenchymal markers (fibronectin and N-cadherin) in colon GEO and HT29 cells. These results indicate that knockdown of Pdcd4 leads to epithelial to mesenchymal transition (EMT). To delineate whether Pdcd4 knockdown promotes cell migration, wound-healing and Boyden chamber migration assays were performed. In wound-healing assay, Pdcd4 knockdown cells showed wound closure approximately 3-fold faster than control cells. In addition, the migration capacity of Pdcd4 knockdown cells is approximately 10-fold higher than that of control cells using the Boyden chamber assay. These findings indicate that knockdown of Pdcd4 promotes migration. To test whether knockdown of Pdcd4 promotes metastasis in vivo, parental, Pdcd4 knockdown, and control cells were injected into the cecal wall (orthotopic implantation) of nude mice (n = 6/group). Six weeks post-injection, samples of lung, liver, lymph node, and cecum were collected and the tumor nodules of each sample were determined. Tumors are formed on cecum in all injected mice. However, only mice injected with Pdcd4 knockdown cells developed hepatic and local lymph node metastases. No pulmonary metastasis was observed. These results indicate that Pdcd4 knockdown promotes metastasis in nude mice. Taken together, our data demonstrated that knockdown of Pdcd4 leads to EMT and promotion of migration and metastasis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1440. doi:10.1158/1538-7445.AM2011-1440
Abstract 1449: A loss-of-function shRNA library screen for the cell invasion-suppressing genes in LNCaP prostate cancer cells
Authors: Su Bing , Baranowski Catherine , Gelman Irwin H. 
Published: June 2012

Abstract
Metastasis remains the primary cause of cancer-related death. Metastasis reduces the 5-year survival rate dramatically, as observed in prostate cancer, and yet, little is known about the genes that control the metastatic process. shRNA libraries are emerging as powerful tools for the identification of genes with specific functions. Here, we describe the successful application of this functional gene-discovery system by identifying genes suppressing tumor invasion, a process that is essential for metastasis. After infecting human prostate cancer cells, LNCaP, with Decode lentiviruses encoding the entire human genomic shRNA library, highly invasive variants were selected using Matrigel invasion assays. After three cycles of selection, we isolated highly invasive clones from 7 shRNA library pools. Using DNA sequence analysis and a database search, we identified five genes previously not associated with control of tumor cell invasiveness: forkhead box O4 (FOXO4), kinesin family member 3B (KIF 3B), signal transducing adaptor molecule (SH3 domain and ITAM motif) 1 (STAM), SUMO1/sentrin specific peptidase 1 (SENP1), and Homo sapiens solute carrier family 17 (SLC17A4). Silencing of FOXO4, a member of Forkhead transcription factors family, by small interfering RNAs indeed increased invasion of LNCaP cells. Reintroducing FOXO4 decreased invasion in the highly invasive prostate cancer cell lines DU145 and CWR22v1. In order to show that increased invasiveness was not a result of a change in survival ability, apoptosis and proliferation were assessed. The results indicate that FOXO4 did not affect proliferation and apoptosis in LNCaP cells. In mammals, the FOXO family comprises four members (FOXO1, FOXO3, FOXO4 and FOXO6). Though FOXO1, 3 and 4 have previously been described as having redundant functions, it appears that FOXO4 has unique metastasis suppressor function in prostate cancer. Additionally, an analysis of web-based gene expression databanks indicates that FOXO4 typically is downregulated in metastatic lesions of breast, prostate and colon cancers when compared to primary lesions. Further characterization of these candidate genes would clarify the complex mechanisms of invasion and metastasis and might reveal new classes of therapeutic targets distinct from known metastatic genes.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1449. doi:10.1158/1538-7445.AM2011-1449
Abstract 145: MicroRNA-361-3p functions as an oncogenic microRNA in human oral cancer cells
Authors: Tanaka Hiroshi , Nakashiro Koh-ichi , Oka Ryota , Nishikawa Yukiko , Goda Hiroyuki , Hamakawa Hiroyuki 
Published: June 2012

Abstract
MicroRNAs (miRNAs) are small non-coding double-stranded RNA with sizes of 20-25 nucleotides, and inhibit protein translation by binding the 3'-untranslated region of target mRNA. Each miRNA can regulate multiple mRNAs and each mRNA can be targeted by a number of miRNAs. In cancer, miRNAs can act as not only tumor suppressor genes but also oncogenes (OncomiR). Most recent study has demonstrated OncomiR addiction in mouse pre-B-cell lymphoma. OncomiR addiction may also provide therapeutic opportunities in human cancers such as oncogene addiction. In this study, we have attempted to identify an OncomiR in human oral cancer cells through functional screening and considered whether targeting miRNA can be possible for cancer therapy. First, we performed functional screening for OncomiR in human oral cancer cells by the use of miRCURY LNATM microRNA Knockdown Library (Exiqon). We transfected 918 locked nucleic acid (LNA) antisense oligonucleotides for specific human mature miRNAs into human oral squamous cell carcinoma cells (GFP-SAS) and salivary gland cancer cells (GFP-ACCM). After transfection for 80 hours, each cell growth was evaluated. LNA antisense oligonucleotides against microRNA-361-3p (LNA-miR-361-3p) showed a remarkable growth inhibition in both types of cells as compared with non-targeting LNA oligonucleotides. We also observed the change of cell morphology, diminution of colony size, and a number of non-adherent cells after transfection of LNA-miR-361-3p. Subsequently, we examined the knockdown effect of LNA-miR-361-3p in GFP-SAS cells by quantitative RT-PCR. Compared with control oligonucleotides, the expression of miR-361-3p was significantly reduced by 71%. These effects of LNA-miR-361-3p were not observed by transfection of DNA or RNA antisense oligonucleotides for miR-361-3p. Next, we transfected synthetic human mature miR-361-3p into GFP-SAS cells to investigate the effect of miR-361-3p overexpression. Cell growth resulted in a significant 20% increase compared with non-targeting control miRNA. Furthermore, co-transfection of LNA-miR-361-3p and its decoy oligonucleotides abrogated the growth inhibitory effect by LNA-miR-361-3p in GFP-SAS cells. These results suggest that miR-361-3p functions as an OncomiR in human oral cancer cells and LNA antisense oligonucleotides are useful and efficient for silencing miRNA. Targeting miR-361-3p with LNA antisense oligonucleotides may be a useful therapeutic approach for patients with oral cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 145. doi:10.1158/1538-7445.AM2011-145
Abstract 1459: Mining for metastasis genes in osteosarcomas from p53 +/R172H mice
Authors: Xiong Shunbin , Suh Young-Ah , Quintás-Cardama Alfonso , Lozano Guillermina 
Published: June 2012

Abstract
Osteosarcoma (OS) is the most frequent bone cancer in young adults. The 5-year relapse free survival rates in nonmetastatic osteosarcomas are up to 65%, while metastatic osteosarcomas are only 10-20%. Therefore, identifying genes involved in OS metastasis is important to risk-stratify patients and enable development of novel therapeutic targets. In mouse models, loss of one p53 allele causes 34% of mice to develop OS without obvious metastasis; however, mice carrying a p53 missense mutation (R172H) develop metastatic OS. To screen for gene expression differences in metastatic potential between p53+/− and p53R172H/+ osteosarcomas, we used Affymetrix Mouse Genome 430 2.0 chips and compared three p53+/− and eight p53R172H/+ primary OS tumors. Two hundred thirteen genes were identified that had a p value &lt; 0.05 and an average fold difference of 2. Only 20 of these genes had reported gene functions that affected cell migration, invasion, cell-cell junctions, or tumor phenotypes, or were selected based not only on statistical significance but also because they were consistently up (or down) regulated in all 8 R172H/+ tumors analyzed. Of these 20 genes, eight were validated by q-PCR in a larger group of tumors; S100A8, S100A9, PLA2G16, Plac8, and MAP kinase-interacting serine/threonine kinase 2 (Mnk2) were elevated while FAT4, FAT3, and Brdw1 showed decreased expression in mutant p53 tumors. To further characterize the functions of these genes in OS metastasis, we chose a metastatic OS cell line (H318) derived from p53R172H/+ tumor that had lost the wild type p53 allele for short hairpin RNAs (shRNAs) knock-down experiments followed by screening for migration and invasion. Three of these genes, PLA2G16, Plac8, and Mnk2, showed effects on migration and invasion in vitro. Further studies led us to focus on PLAG2G16. Knock-down of PLA2G16 showed decreased migration, invasion and proliferation. Additionally, we also subcutaneously injected PLAG2G16 knock-down cells into congenic wild type mice. Remarkably these cells showed dramatic decrease in tumor progression and metastasis. These effects were reproducible in another cell line with a different p53 mutant, 4T1. To determine whether we could make a non-metastatic cell adopt metastatic properties by simply expressing PLA2G16, we expressed FLAG-tagged PLA2G16 in two p53-null cell lines that lacked metastatic potential. These cells showed a 2-fold and 7-fold increase in invasion in culture, respectively. These preliminary data suggest that the expression of PLA2G16 in mutant p53 cell lines contributes to migration, invasion, and metastasis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1459. doi:10.1158/1538-7445.AM2011-1459
Abstract 1462: Anti-metastasis effect of novel ALK5 inhibitor in both breast cancer cells in vitro and 4T1 xenograft mice in vivo
Authors: Son Jee , Yoon Eun , Kim Dae-Kee , Sheen Yhun Y. 
Published: June 2012

Abstract
We have synthesized novel ALK5 inhibitors and investigated their effects of on breast cancer cells as well as tumor bearing MMTV/cNeu transgenic mice and 4T1 orthopathologically xenograft balbC mice. The treatment of ALK5 inhibitors into breast tumor bearing MMTV/cNeu transgenic mice and orthotopically injected mice inhibited the numbers of nodules in the lung compared to that of untreated animal. The level of ß-casein in the lung of the breast tumor bearing MMTV/cNeu transgenic mice and 4T1 orthotopically xenograft mice were decreased by ALK5 inhibitor treatment. Zymogragh showed that the levels of MMP2 and MMP9 were decreased in the lung and breast tumor of ALK5 inhibitors treated breast tumor bearing MMTV/cNeu transgenic mice and 4T1 orthotopically xenograft mice. The action mechanisms of new ALK5 inhibitors were investigated in both breast cancer cells and breast cancer mice model. TGFß signaling, phosphorylated smad2/3 based from the western blot analysis in vitro and in vivo as well as confocal microscopic analysis in vitro was decreased by ALK5 inhibitors. And also, new ALK5 inhibitors inhibited the TGFß action on wound healing and cell invasion based on wound healing assay and invasion assay. This data strongly argue that ALK5 inhibitors have anti-metastasis effects via inhibiting ALK5 activity in vivo and in vitro. In order to gain further insight into the mechanism of ALK5 inhibitor, we have carried out experiment to examine the effects of ALK5 inhibitor in human breast cancer MDA-MB-231 cell. TGFß stimulated mesenchymal markers of epithelial mesenchymal transition (EMT), such as Snail, TWIST, N-cadherin and these were inhibited by ALK5 inhibitor concomitant treatment. Also, TGFß increased tumor invasion markers such as MMP2, and MMP9 which were inhibited by ALK5 inhibitor concomitant treatment. In summary, ALK5 inhibitors have anti-metastatic effect on human breast cancer cells as well as tumor bearing MMTV/cNeu transgenic mice.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1462. doi:10.1158/1538-7445.AM2011-1462
Abstract 1469: Mechanisms of oncostatin M (OSM)-mediated breast cancer metastasis to bone: Evidence for a role in osteoclastogenesis
Authors: Bolin Celeste M. , Tawara Ken , Sutherland Caleb , Anderson Robin , Jorcyk Cheryl 
Published: June 2012

Abstract
Oncostatin M (OSM) is an interleukin-6 (IL-6)-family cytokine that has been implicated in a number of biological processes including the induction of inflammation and modulation of the extracellular matrix. OSM was initially shown to inhibit the proliferation of breast cancer cell lines in vitro and has been evaluated as a potential cancer therapy. However, evidence in the literature and our data suggest that OSM may actually promote tumor invasion and metastasis. Using the orthotopic 4T1.2 mouse mammary model of metastasis, we have investigated the ability of OSM to enhance the formation of metastases in organs such as lung and bone in vivo. OSM expression was knocked down using shRNA in 4T1.2 cells, which endogenously express both OSM and its receptor. These 4T1.2-OSM cells were orthotopically injected into Balb/c mice and resulted in a 98% decrease in metastasis to bone and a 55% decrease in metastasis to lung compared to that of 4T1.2-Lac Z control cells. Metastases were quantified using qPCR to detect the vector neomycin resistance gene in post-mortem organ samples. In this study we investigate the specific cellular mechanisms that might be important for tumor cell-derived OSM promotion of metastasis to bone, such as hypoxia-inducible factor 1 alpha (HIF1α) and vascular endothelial growth factor (VEGF). An in vitro model was developed using the pre-osteoclast cell line (RAW 264.7) co-cultured with 4T1.2 mouse mammary tumor cells treated with and without recombinant OSM. Osteoclastogenesis of co-cultured RAW 264.7 cells was measured by staining for differentiated osteoclasts using the TRAP (tartrate-resistant acid phosphatase) assay and was found to increase with OSM treatment. Additionally, suppression of HIF1α expression by siRNA resulted in a 76% decrease in OSM-induced osteoclastogenesis. As RAW 264.7 cells do not express the OSM receptor beta (OSMRβ) necessary for OSM signaling, we suggest that this inhibition of osteoclast differentiation is via an autocrine signaling mechanism in the 4T1.2 cells that initiates the secretion of osteoclast differentiation factors including VEGF. Currently, we are investigating what these secreted factors from 4T1.2 cells are that affect RAW 264.7 cell differentiation and activity. Our results suggest that OSM might be an important therapeutic target in the prevention of metastatic breast cancer invasion of bone. Funded by ACS RSG-09-276-01-CSM, Susan G Komen for the Cure KG100513, and NIH/NCRR P20RR016454.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1469. doi:10.1158/1538-7445.AM2011-1469
Abstract 1475: Role of FcγRIIB in metastatic melanoma and rhabdomyosarcoma
Authors: Lu Andrew J. , Yu Yanlin , Merlino Glenn 
Published: June 2012

Abstract
FcγRIIB, known as immunoglobulin gamma Fc region receptor II-b, is a low affinity surface receptor protein for IgG in hematopoietic cells. As an inhibitory receptor, FcγRIIB contains an immunoreceptor tyrosine-based inhibition motif (ITIM) in their cytoplasmic tails that transduces an inhibitory signal on coligation with the activating receptors. FcγRIIIb is anchored to the plasma membrane via a C-terminus-linked GPI moiety. Present exclusively on human neutrophils, it plays a predominant role in binding of immune complexes. Its co-aggregation with FcγRIIa activates phagocytosis, degranulation, and the respiratory burst leading to destruction of opsonized pathogens. Activation of neutrophils leads to secretion of a proteolytically cleaved soluble form of the receptor corresponding to its two extracellular domains. Soluble Fc RIIIb exerts regulatory functions by competitive inhibition of Fcγ R-dependent effector functions and via binding to the complement receptor CR3. Dysregulation of FcγRIIB can promote the susceptibility and severity of several organ-specific and systemic autoimmune diseases invivo. Studies have recently shown that FcγRIIb increased constitutively in malignant lymphocytes and upregulated ectopically melanoma. Using cDNA microarray analysis, we have found that FcγRIIb is upregulated in metastatic melanoma and rhabdomyosarcoma (RMS). These results suggest that FcγRIIb maybe involved in regulation of progression to metastatic state in tumor.To study the role of FcγRIIb in metastatic diseases; we established model systems which stably express wild-type and mutants FcγRIIb in melanoma B16 and RMS772 cells. Cell colonies stably expressing FcγRIIb were selected and tested in vitro and in vivo. Our data showed that expression of FcγRIIb inhibited cell proliferation and caused a noticeable change in cell morphology, but did not affect cell motility and invasiveness. However, overexpression of FcγRIIb significantly stimulated lung metastasis of both melanoma and RMS cell lines. Our data suggest that over-expression of FcγRIIb promotes metastasis in melanoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1475. doi:10.1158/1538-7445.AM2011-1475