bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3359: Glucose regulated protein78, a putative head and neck cancer initiating cells marker
Authors: Wu Meng-Ju , Lo Jeng-Fan , Yu Cheng-Chia 
Published: February 2011

Abstract
Background: Head and neck squamous cell carcinoma (HNSCC) is a highly lethal cancer that contains cellular and functional heterogeneity. Previously, we enriched a subpopulation of highly tumorigenic head and neck cancer initiating cells (HN-CICs) from HNSCC cells (HNSCCs) using tumor sphere formation approach. GRP78, a stress-inducible endoplasmic reticulum (ER) chaperone, has been reported to play a role in the maintenance of embryonic stem cells and was up-regulated in enriched HN-CICs. However, the molecular mechanisms mediated by GRP78 to operate the physiological characteristics in HN-CICs remain unclear. Herein, we determined the critical role of GRP78 in the maintenance of stemness characteristics and tumorigenic phenotype in HNSCCs.
Methods: First, Affymatrix microarray and two-dimensional differential gel electrophoresis (2-D DIGE) proteomic analyses were applied to identify GRP78 and membrane associated GRP78 (memGRP78) as a putative marker of HN-CICs. Flow cytometry cell sorting was used to isolate memGRP78+ cells and memGRP78− cells for evaluating CICs properties. Down-regulation of GRP78 expression in HNSCCs and HN-CICs were achieved by lentiviral-mediated small hairpin RNA interference (shRNAi), and the stemness characteristics in GRP78-knockdown HN-CICs were elucidated. In addition, in vitro tumorigenic properties between GRP78-knockdown and control HN-CICs were determined. The in vivo tumorigenicity of GRP78-knockdown HN-CICs was evaluated by xenotransplantation assay. Finally, we examined the correlation on expression of GRP78 and stemness genes in HNSCC patient tissues by immunohistochemical staining.
Results: We identified that GRP78/memGRP78 was significantly up-regulated in enriched HN-CICs. Subsequently, memGRP78+ HNSCCs displayed CICs properties. Lentiviral mediated knockdown of GRP78 significantly reduced expression of stemness genes in HN-CICs and HNSCCs, but enhanced the differentiation capability of HN-CICs. Overall, down-regulation of GRP78 lessened tumorigenicity of HN-CICs both in vitro and in vivo.
Conclusion: Our studies first elucidated the crucial role of GRP78 in the maintenance of stemness and tumorigenicity of HN-CICs. Notably, targeting GRP78 signaling might be a potential therapeutic target for HNSCC by eliminating CICs and memGRP78 could be a novel surface biomarker for isolation HN-CICs.
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 3359.
Abstract 3360: Inhibition of ALDH activity prevents the maintenance and expansion of cancer stem cell-like population in a mouse model of breast cancer
Authors: Kim Ran-Ju , Park Jeong-Ran , Roh Kyung-Jin , Nho Kyoung-Jin , Kim Soo-Rim , Lee Yoo-Kyung , Nam Jeong-Seok 
Published: February 2011

Abstract
The cancer stem cell (CSC) hypothesis proposes that CSCs are the root of cancer and cause cancer metastasis and recurrence. High activity of aldehyde dehydrogenase (ALDH) has been recognized as a marker for normal and malignant stem cells. It has been also known that ALDH activity is important for multiple biological activities including drug resistance, cell differentiation, and oxidative metabolism. In this study, we focused on the molecular mechanism of ALDH activity in CSC dynamics. To address the underlying mechanism, we have used the 4T1 mouse model of breast cancer. We found that ALDHpos cells showed a high increase of the stem cell-like properties, such as sphere forming ability, expression of stem markers, and tumor initiation ability in vivo, when compared with the counterparts. Blockade of ALDH activity suppressed these properties of CSC. Especially, the high activity of ALDH was shown to enhance CSC properties through up-regulating Oct-4 expression that is dependent on oxygen-related transcription factor. Therefore, these findings suggest that the selective targeting of ALDH activity may be useful for stem specific cancer therapies.
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 3360.
Abstract 3377: CXCL13-directed therapy against bone metastasis in hormone-refractory prostate cancer
Authors: Lillard James W. , Singh Rajesh , Singh Shailesh , Sharma Praveen K. 
Published: February 2011

Abstract
Metastasis is responsible for most prostate cancer (PCa) related deaths; therefore, therapies designed to prevent or abrogate the spread of cancer cells and prognostic tests to better predict outcomes are greatly needed. Chemokines and their receptors are thought to play key roles in this multi-factorial process. We have recently reported, chemokine receptor CXCR5 and its ligand CXCL13 expression positively correlates with prostate tumor staging. We have also noted differential expression of CXCR5 by PCa cell lines (LNCaP, C4-2B, DU145, and PC3). By virtue of the presence of elevated CXCL13 levels in patient serum, CXCL13 secretion by bone marrow endothelium, and expression of CXCR5 on the surface of PCa cells, we hypothesized that gradient-dependent CXCR5-CXCL13 interactions are responsible in part for PCa cell bone metastases and inhibition of this axis may prove beneficial for prevention of bone metastasis and tumor progression. Luciferase-expressing PC3 cells were injected into the right carotid artery or directly into the tibia of nude mice. Before and after the development of bone metastases, groups were treated with control or anti-CXCL13 antibodies every third day and monitored for tumor progression or regression by non-invasive bioluminescent and microCT in vivo imaging. We demonstrate CXCL13 is present in bone marrow of xenograft tumor-bearing mice following intra-cardiac /intra-tibial injection of PC3 cells. This hormone-refractory PCa cell line established skeletal (osteolytic) metastases and tumor growth, but CXCL13 blockade significantly delayed prostate tumor formation, osteolysis, and spread to bones as well as growth, than compared to mice treated with control antibody. In conclusion, our study shows that the CXCL13-CXCR5 axis supports PCa bone metastasis and growth.
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 3377.
Abstract 3385: A craniectomy open window model for longitudinal subcellular imaging of cancer cell nuclear-cytoplasmic dynamics in the brain
Authors: Momiyama Masashi , Endo Itaru , Hoffman Robert M. 
Published: February 2011

Abstract
Brain metastasis is a lethal step in breast and other cancers. However, there has not been a method to image brain metastasis at the single-cell level in vivo. In order to visualize metastatic single cancer cell nuclear-cytoplasmic dynamics in the brain, dual-color Lewis Lung carcinoma (LLC) cells, labeled with GFP in the nucleus and RFP in the cytoplasm, were injected into the right internal carotid artery of nude mice. A craniectomy open window was made over the right parietal bone. The animals were imaged at the subcellular level through the craniectomy open window with the Olympus OV100 Small Animal Imaging System under high magnification. Metastatic dual-color LLC cells could be visualized at the subcellular level in the brain. Metastatic colony progression, tumor micro vessels, and cancer cell mitosis apoptosis were imaged. Imaging could be carried out for at least two weeks through the craniectomy window. The novel mouse model for subcellular imaging of cancer cells in the brain will enable a deeper understanding of brain metastases and cancer cell nuclear-cytoplasmic dynamics in the brain.
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 3385.
Abstract 3386: In vivo imaging of inflammation- and tumor-induced lymph node lymphangiogenesis by immuno-positron emission tomography
Authors: Mumprecht Viviane , Honer Michael , Vigl Benjamin , Proulx Steven , Trachsel Eveline , Kaspar Manuela , Banziger-Tobler Nadja , Schibli Roger , Neri Dario , Detmar Michael 
Published: February 2011

Abstract
Metastasis to regional lymph nodes is a prognostic indicator for cancer progression. There is a great demand for sensitive and non-invasive methods to detect metastasis to the lymph nodes. While conventional in vivo imaging approaches have focused on the detection of cancer cells, lymphangiogenesis within tumor draining lymph nodes might be the earliest sign of metastasis. In mouse models of lymph node lymphangiogenesis, we found that systemically injected antibodies to lymphatic epitopes accumulated in the lymphatic vasculature in tissues and lymph nodes. Using a 124I-labeled antibody against the lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), we imaged, for the first time, inflammation-and tumor-draining lymph nodes with expanded lymphatic networks in vivo by positron emission tomography. This method might open up new avenues for the early detection of metastases and the images obtained might be used as biomarkers for the progression of diseases associated with lymphangiogenesis.
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 3386.
Abstract 3389: SLPI promotes EMT in HaCaT cells
Authors: ElMasri Wafic M. , Yu Minshu , Virador Victoria M. , Kohn Elise C. 
Published: February 2011

Abstract
The majority of solid tumors are carcinomas. To invade, carcinomas must lose cell-cell adhesion and acquire motility: a process termed epithelial-to-mesenchymal transition (EMT). EMT is a highly conserved cellular program that enables polarized, immotile epithelial cells to convert to motile mesenchymal-like cells. Secretory leukocyte protease inhibitor (SLPI; 12-14 kD) is genomically, transcriptionally, and translationally upregulated in epithelial ovarian cancer. SLPI is anti-inflammatory, mediates wound healing, and stimulates cellular proliferation, angiogenesis, invasion, and metastasis. We previously showed that SLPI binds to and protects progranulin (pgrn), a survival factor for ovarian cancer, from elastase-mediated degradation. We also showed that overexpression of SLPI mediates paclitaxel resistance in 1A9 and HeyA8 ovarian cancer cells. We hypothesize that SLPI promotes metastasis via induction of EMT, which can be modulated by inhibition of its protease inhibitory (PI) activity or binding to pgrn. We stably transfected immortalized human skin keratinocytes (HaCaT cells) with wild type SLPI and three mutants: F-SLPI [loss of PI activity], KRK-SLPI [loss of pgrn binding], and F-KRK-SLPI [double mutant]. Overexpression of SLPI or the mutants did not transform the immortalized HaCaT cells; however, it increased colony proliferation, anchorage-independent growth, and resistance to anoikis. The SLPI mutants that do not bind pgrn were more aggressive. Transfection with SLPI and its mutants markedly decreased cell-cell adhesion, altered cellular adhesions to extracellular matrix components, and led to increased cell motility and wound healing in transfected HaCaT cells. SLPI and its mutants enhanced TGF-β induced EMT and effectively blocked TGF-β mediated growth inhibition of HaCaT cells. Thus, SLPI overexpression advances an EMT phenotype in immortalized HaCaT epithelial cells. We continue elucidating the role of SLPI in EMT and the mechanism of its interaction with proganulin for future therapeutic targeting in epithelial ovarian carcinoma.
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 3389.
Abstract 3392: Heat shock protein 27 increases metastasis of human head and neck squamous cancer cells in vitro
Authors: Zhu Zhenkun , Xu Xin , Yu Yanke , Graham Martin , Liu Gangli , Prince Mark , Carey Thomas , Sun Duxin 
Published: February 2011

Abstract
The small heat shock protein 27 (Hsp27) is a molecular chaperone that is involved in a variety of cellular functions in cancer cells. The purpose of this research is to study the function of Hsp27 in metastasis of head and neck squamous cancer cells. The expression of Hsp27 in primary and metastatic head and neck cancer cells was determined using real-time PCR and western blotting. The siRNA knockdown of Hsp27 was performed in metastatic head and neck cancer cells using in vitro transfection. The proliferation of the primary and metastatic head and neck cancer cells were evaluated using MTS proliferation assay. The metastatic potential was determined using both migration assay and invasion assay in metastatic head and neck cancer cells after siRNA silencing of Hsp27. MTS proliferation showed that both primary (UM-SCC-22A) and metastatic (UM-SCC-22B) head and neck cancer cells have similar proliferation rate from 24-48 hrs. However, the metastatic head and neck cancer cells (UM-SCC-22B) showed more than 2-fold migration ability and more than 3-fold invasion ability than primary head and neck cancer cells (UM-SCC-22A). Real-time PCR demonstrated that Hsp27 mRNA is 22-fold higher in metastatic UM-SCC-22B than primary UM-SCC-22A. Similarly, Western blotting exhibited that primary UM-SCC-22A did not show any detectable levels of Hsp27, while metastatic UM-SCC-22B showed significant high levels (&gt; 40-fold) of Hsp27. siRNA of Hsp27 knocked down expression of Hsp27 by more than 5-fold in mRNA level and 23-fold in protein levels in metastatic head and neck cancer cells UM-SCC-22B. Furthermore, siRNA knockdown of Hsp27 decreased metastasis of UM-SCC-22B by more than 50% in cell invasion assay. These data suggest that Hsp27 may regulate metastatic potential of head and neck squamous cancer cells. Silencing Hsp27 may decrease metastatic potential of head and neck squamous cancer cells.
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 3392.
Abstract 3395: Role of ErbB3 signaling in tumor cell motility and metastasis
Authors: Smirnova Tatiana , Wyckoff Jeffrey , Segall Jeffrey E. 
Published: February 2011

Abstract
The major cause of death for most cancers, including that of the breast, is from metastasis. One of the trends in anticancer therapy research has recently been inhibiting the epidermal growth factor receptor (EGFR, ErbB) family that is part of the subclass I of the receptor tyrosine kinase superfamily. ErbB receptors are involved in activating such key pathways as PI3-kinase and Ras/MAP kinase. Close to 30% of highly invasive human breast cancers show elevated expression/activity of the ErbB2 receptor, a marker for poor prognosis and decreased disease-free survival. The preferred heterodimerization partner of ErbB2 is ErbB3. Previous data from our laboratory has shown that increasing expression of ErbB3 caused a significant increase in intravasation and metastasis without affecting primary tumor growth/formation. The ligand for ErbB3 is Heregulin Beta 1 (HRGβ1) and its binding leads to heterodimerization with other ErbB's, followed by activation of signaling pathways that result in cell chemotaxis and movement. Knowing that ErbB3 is important for metastasis, our goal is to determine which signaling pathway downstream of ErbB3 is responsible for metastasis as well as what cellular property (e.g. motility or chemotaxis) and which step of metastasis is affected (invasion, intravasation, lung seeding).
Stably transduced MTLn3 cells (rat mammary adenocarcinoma cell line) overexpressing WT and mutant versions of ErbB3 defective in PI3K, MAPK and Grb7 signaling were used for in vitro and in vivo experiments examining the role of ErbB3 signaling pathways. WT and mutant versions of ErbB3 were compared in their ability to chemotax in vitro. Orthotopic injection of the WT and mutant MTLn3 cell lines into the mammary fatpads of SCID mice has allowed us to examine their in vivo invasion potential by measuring the ability of cells to migrate out of the primary tumor towards a gradient of HRGβ1, intravasation - number of cells able to enter blood stream, and live imaging using multiphoton microscopy which will allow to see tumor cell polarization and movement towards blood vessels. In addition, tail vein injection tested the ability of cells to seed the lungs.
While previous data from our laboratory has shown that ErbB3 overexpression significantly enhances metastasis, it is still not known how. Preliminary results from these experiments suggest a key role for tyrosine residues on the ErbB3 receptor that couple to the PI3-kinase pathway in tumor cell motility 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 3395.
Abstract 3413: Tumor-specific transcriptional control networks regulating DNA replication genes in Ewing's sarcoma
Authors: Smrzka Oskar W. , Pöhler Christina , Kauer Maximilian , Westermann Frank , Kovar Heinrich 
Published: February 2011

Abstract
Surveillance of DNA replication licensing is often perturbed in cancer cells allowing for genomic aberrations. Although this process contributes to cellular transformation, it is not well understood to what extent and how oncogenes might deregulate genes involved in DNA replication and in the control of replication licensing. Previous findings on the EWS-FLI1 fusion oncogene (which is the genetic hallmark Ewing's sarcoma), and our recent findings on MYC targets in this aggressive childhood tumor suggested that both these oncogenes constitute a regulatory feed-back loop. Our gene expression data from Ewing's cells in which MYC had been knocked down, we propose that MYC mediates at least part of the oncogenic EWS-FLI1 functions since it controls most essential biological functions required for cell proliferation. Gene expression correlation and gene set enrichment analysis in tumors and cell lines suggests the MYC/EWS-FLI1 loop as a central regulator in a regulatory network that controls DNA replication. To further narrow down the target gene repertoire and to identify direct transcriptional targets, we performed a genome wide chromatin-immunoprecipitation study using an anti MYC antibody in combindation with ChIP/CHIP analysis. We further extended our model whereby the core EWS-FLI1/MYC feedback loop could be linked to other candidate transcriptional regulators of DNA replication. Several replication licensing genes including MCM, ORC or licensing control genes such as CDT1 and CDC6 were found to be under direct and/or indirect control of the MYC/EWS-FLI1 loop and their associated transcription factor network. A subset of DNA replication genes is particularly deregulated in Ewing's cells when compared to mesenchymal progenitor cells that are considered the tissue of origin of Ewing's sarcoma. When comparing Ewing's sarcoma with other childhood tumors such as e.g. neuroblastoma, we found Ewing's-specific versus more general regulatory connections between the MYC/EWS-FLI1 loop and DNA replication genes. Together, our data provide first insight into a newly defined MYC/EWS-FLI1-driven regulatory network underlying transcriptional DNA replication control.
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 3413.
Abstract 3415: Therapeutic targeting of the ASPL-TFE3 gene fusion in ASPS-1, a novel cell line derived from metastatic alveolar soft part sarcoma (ASPS)
Authors: Vistica David T. , Kenney Susan , Burkett Sandra , Hollingshead Melinda , Borgel Suzanne , Butcher Donna , Schrump David S. , Shoemaker Robert H. 
Published: February 2011

Abstract
Alveolar soft part sarcoma (ASPS) is a rare soft tissue sarcoma primarily affecting young children and adolescents. ASPS is characterized by a nonreciprocal chromosomal translocation, der(17)t(X;17)(p11;q25), in which the N-terminal region of the alveolar soft part locus (ASPL) gene, located at 17q25, is fused to the C-terminal region of the transcription factor E3 (TFE3), located at Xp11. Two alternative fusion junctions have been observed resulting in the expression of 2 distinct fusion transcripts, ASPL-TFE3 type 1 and 2, and their respective proteins which function as hybrid transcription factors. Recently we have described the first xenograft model of ASPS, established from a lymph node metastasis derived from a female patient expressing the ASPL-TFE3 type 1 fusion, in NOD.SCID mice (J. Pediatr. Hematol. Oncol 31:561, 2009) and an ASPS cell line, ASPS-1, derived from it (Proc. Amer. Assoc, Cancer Res. 50:978, 2009). We report here our efforts to target the ASPL-TFE3 type 1 gene fusion (CGG GAG CGG CTG CCT GTG TCA) in ASPS-1 cells using siRNA directed against its nucleotide sequence and compared results with siRNA directed against the ASPL-TFE3 type 2 gene fusion (CGG ATT GAT GAT GTC ATT GAT). ASPL-TFE3 type 1 and 2 siRNA were evaluated in vitro in ASPS-1 cells, which express the ASPL-TFE3 type 1 gene fusion and protein, at concentrations ranging from 1-50 nM and treatment times ranging from 3-12 days. These results indicate that the ASPL-TFE3 type 1 siRNA, but not the ASPL-TFE3 type 2 siRNA or a control siRNA not known to target any human gene, was effective in reducing the ASPL-TFE3 type 1 fusion transcript, the ASPL-TFE3 type 1 fusion protein and retarding the growth of ASPS-1 cells. Importantly the ASPL-TFE3 type 1 siRNA down regulated several signature ASPS genes (BMC Cancer 9:22, 2009) including those involved in angiogenesis of this highly vascular tumor (ANGPTL2, MDK, c-MET, and TIMP-2). Additionally, PCSKI, a proprotein convertase responsible for processing of neuropeptides, growth factors and receptors, and several tissue restricted markers including ITGB1BP3, was strikingly down regulated. Together these results suggest that the ASPL-TFE3 fusion gene and its fusion protein play an important role in pathways involved in the growth of ASPS and present potentially exploitable targets for development of novel therapeutics.
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 3415.