bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5121: Laminin 511 on human gastric carcinoma cells is a ligand for hepatic asialoglycoprotein receptor involved in liver metastasis
Authors: Ueno Suguru , Nodera Yoshiaki , Gomez Laura Santos , Higashi Nobuaki , Irimura Tatsuro 
Published: February 2011

Abstract
– Background and Aim – Gastric cancer often metastasizes to the liver and galactose-type lectins were previously proposed to play an important role in hepatic metastases because intravenous administration of galactose at the time of surgical removal of gastric cancer was reported to extend the survival of the patients. Asialoglycoprotein receptor (Asgpr) is a galactose-type calcium-type lectin and a primary candidate molecule involved in this process. Variant cell lines of human gastric carcinoma, AZ521 cells, were obtained by sorting for high and low levels of cell surface bindings of recombinant Asgpr and designated as AZhigh and AZlow cells, respectively. The present report is to assess the metastatic potential of these cell lines and determine the ligand for Asgpr on the surfaces of these gastric carcinoma cells.
– Materials and Methods – AZhigh and AZlow cells were injected into nude mice via portal vein and metastatic growth in the liver were evaluated 14 days later. AZhigh and AZlow cells were biotinylated at the cell surfaces and the lysates were prepared. Components bound to immobilized Asgpr were collected and analyzed by SDS-PAGE then differentially expressed components were subjected to MALDI-TOF MS analysis after trypsin digestion. Specific monoclonal antibodies specific for particular components such as laminin α5 chain were used to confirm the identified proteins from the carcinoma cells.
– Results and Discussion – Metastatic growth in the liver was more prominent with AZhigh cells than AZlow cells. AZhigh cells adhered to immobilized Asgpr more rapidly than AZlow cells. From components eluted from immobilized Asgpr, laminin α5, β1, and γ1 chains were identified. By flow cytometric analysis, anti-human laminin α5 antibody bound to AZhigh cells but the binding to AZlow were negligible. Similar difference was observed by immunoprecipitation. Laminin α5 chain was also in the culture supernatants of AZhigh cells, but not those of AZlow cells. These results suggest that laminin 511 differentially expressed between AZhigh and AZlow cells and acted as the ligands for Asgpr. Further study focusing on laminin 511 will be needed for elucidating the mechanism of hepatic metastases of gastric cancer.
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 5121.
Abstract 5125: The identification of Gelsolin as a potential binding partner of Nm23
Authors: Marino Natascia , Marshall Jean-Claude A. , Collins Joshua , Zhou Ming , Veenstra Timothy , Steeg Patricia 
Published: February 2011

Abstract
Nm23 was the first metastasis suppressor gene to be identified. To better understand the biological mechanism leading to its anti-metastatic properties, we have investigated new potential binding-proteins of Nm23. Using Mass-spectrometry, we analyzed proteins obtained with co-immunoprecipitation of Nm23 in a mouse mammary cancer cell line overexpressing the human and murine forms of Nm23 (4T1-Nm23H1-flag and 4T1-Nm23M1-flag). Co-immunoprecipitations were also performed from primary tumors and liver metastases obtained from injection of these cell lines into Balb/C mice. Several proteins were found to bind Nm23, both in vitro and in vivo specimens. In addition to previously published Nm23 interacting proteins, we identified new binding partners including the actin-binding protein Gelsolin.
Using immunoprecipitation assays, the interaction between Gelsolin and Nm23 was validated in a murine cell line (4T1- Nm23H1/M1 clones) and then in human breast carcinoma cell lines with low (MCF-7) and high metastatic potentials (MDA-MB-435, MDA-MB-231). In the highly metastatic MDA-MB-231 cell line, the interaction was observed only after the overexpression of Nm23 in the system. These results suggest that a Nm23-gelsolin interaction may only take place when relatively high levels of Nm23 are expressed.
Moreover, we observed that this interaction involves not only the native form of Gelsolin but also Gelsolin-fragments, NH2-terminal and COOH-terminal, which are generated by the action of caspase-3 cleavage. Full-length Gelsolin binds and severs actin polymers in a Ca2+-dependent manner, whereas caspase-3-cleaved Gelsolin severs actin polymers independent of Ca2+. The overexpression of the NH2-terminal fragment has been shown to induce apoptosis, whereas the COOH Terminal fragment has been shown to have an anti-apoptotic effect. We are therefore interested in exploring which Gelsolin-fragment may be specifically binding to Nm23, in order to determine the biological function regulated by this interaction. Our results show a novel Nm23 binding partner, Gelsolin, which is involved in the actin-cytoskeleton regulation and may, in part, explain the motility inhibitory activity of Nm23. The exact interactions between Nm23 and Gelsolin are currently being explored. In particular we are evaluating the role of this interaction in the anti-metastatic effects of Nm23, both human and murine.
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 5125.
Abstract 5128: Identification of RhoGEFs within the TWEAK-R (Fn14)-Rac1 signaling pathway that mediate glioblastoma cell invasion
Authors: Ennis Matthew J. , McDonough Wendy S. , Chan Amanda , Symons Marc H. , Winkles Jeffrey A. , Salhia Bodour , Loftus Joseph C. , Tran Nhan L. 
Published: February 2011

Abstract
Glioblastoma multiforme (GBM) is the most malignant primary adult brain tumor. Despite efforts at surgical resection of the glioma mass, invasive cells are always left behind and the tumor will inevitably recur and kill the patient. As such, novel therapeutics targeting pro-invasive factors could improve neurological outcomes and survival for these patients. This requires a detailed understanding of the mechanisms driving glioma migration and invasion. We have been investigating whether the multifunctional cytokine tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) regulate glioma cell invasive activity. We have previously demonstrated that Fn14 expression was elevated in the invasive rim of GBM specimens and migrating glioma cells in vitro. The Fn14 signaling axis is known to drive glioma invasion via Rac1. We have previously reported that Ect2, a guanine nucleotide exchange factor (GEF) for Rho family GTPases, including Rac1 and Cdc42, is overexpressed in GBM, and that overexpression of Ect2 correlates directly with tumor grade and inversely with patient survival. In this study we show that Ect2 regulates Rac1 activation downstream of Fn14. Depletion of Ect2 by siRNA duplexes abrogates Fn14-induced Rac1 activation and subsequent glioma cell migration and invasion. We also found that Cdc42 activation by TWEAK is directly mediated by Ect2. Interestingly, depletion of Cdc42 expression impairs TWEAK-induced Rac1 activation and also results in a significant reduction of glioma cell migration and invasion. This suggests that Cdc42 is, in part, important for Rac1 activation downstream of the TWEAK-Fn14 signaling pathway and argues that another GEF(s) may be involved in the Fn14-Rac1 signaling axis. Recently, we have identified Trio as an additional GEF that activates Rac1 downstream of Cdc42. It is also known that Trio expression correlates directly with brain tumor grade and inversely with patient survival. siRNA-mediated depletion of Trio inhibits TWEAK-induced Rac1 activation but not TWEAK-induced Cdc42 activation. Therefore, delineating the mechanisms of Fn14-RhoGEF-RhoGTPase signaling pathway, may lead to identification of novel targets that can serve as possible points of therapeutic intervention. (Supported by NIH R01-CA130940)
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 5128.
Abstract 5130: Src and Caveolin-1 reciprocally regulate metastasis via Rho Kinase
Authors: Thomas Shibu , Overdevest Jonathan B. , Nitz Mathew , Williams Paul , Schwartz Martin A. , Theodorescu Dan 
Published: February 2011

Abstract
In human bladder cancer, overexpression of Caveolin-1 (Cav-1) and downregulation of Src expression and kinase activity correlate with aggressive behavior suggesting they may have causal and perhaps interactive roles in this process. Here we show that Cav-1 and Src are reciprocally expressed in the same tumors, suggesting they act on a similar pathway. RNAi mediated Cav-1 depletion or expression of constitutively active Src in invasive human urothelial cancer cells UMUC-3 and KU-7 resulted in loss of stress fibers and reduced capacity to migrate. Cav-1 depletion was associated with loss of pY14 Cav-1 while increased p190RhoGAP was seen with Src over-expression while both led to a significant reduction in RhoA and RhoC levels and activity. Conversely, expression of Cav-1 but not the non-phosphorylatable mutant of Cav-1 or suppression of Src using PP2 or Src RNAi in noninvasive human urothelial RT4 cancer cells, increased RhoA and RhoC GTP and cell migration. Use of ROCK inhibitor Y27632 in RT4 cells completely abolished enhanced migration induced by Cav-1 expression or that associated with Src inhibition. Furthermore, metastatic lung colonization of UMUC-3 cells expressing constitutively active Src or depleted of Cav-1 was significantly reduced while having marginal effect on subcutaneous tumor growth. Moreover, ROCK inhibitor prevented bladder cancer lung metastasis in vivo. Our findings indicate Src is metastasis suppressor protein in bladder cancer and describe a novel relationship between Cav-1 and Src in regulating RhoA and RhoC providing a unifying molecular mechanism for prior descriptive studies suggesting a role for these proteins in bladder cancer progression.
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 5130.
Abstract 5132: 14-3-3sigma coordinates breast tumor invasion by regulating cytoskeletal dynamics
Authors: Boudreau Aaron , Geyer Felipe C. , Wang Daojing , Reis-Filho Jorge S. , Bissell Mina J. 
Published: February 2011

Abstract
14-3-3sigma was initially described as a tumor suppressor silenced in about 80% of breast tumors. Surprisingly however, in two independent culture models of breast cancer progression, we discovered 14-3-3sigma expression increased as cells transition towards malignancy, and that it contributed to motility and tumor invasion into surrounding tissues in vivo. Immunohistochemical analysis showed that 14-3-3sigma expression preferentially identified a subset of invasive breast carcinomas, and in independent breast cancer patient cohorts, 14-3-3sigma correlated with poor clinical outcome. We observed several lines of evidence that 14-3-3sigma regulates cytoskeletal architecture in cells, providing a molecular mechanism by which 14-3-3sigma may coordinate tumor progression and invasion.
Funding is provided by a DOD BCRP Predoctoral Fellowship and a CBCRP Dissertation Award to AB, as well as DOE, NCI, NIH, and DOD grants to MJB.
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 5132.
Abstract 5134: Mechanistic dissection of EWS-FLI impact on Ewing's sarcoma cell behavior
Authors: Chaturvedi Aashi , Lessnick Stephen L. , Beckerle Mary C. 
Published: February 2011

Abstract
Ewing's sarcoma is caused by the oncogenic fusion of the EWS and FLI genes to encode a chimeric EWS-FLI protein product. The disease is often metastatic at presentation. This study aims to define the molecular mechanism by which the EWS-FLI oncoprotein influences metastatic potential by testing the impact of EWS-FLI expression on cytoarchitecture, adhesion, and migration of Ewing's sarcoma cells. We compared the behavior of A673 Ewing's sarcoma cells with A673 cells in which we knocked down expression of EWS-FLI by RNA-interference. Knock-down of EWS-FLI results in enhanced cell spreading and the establishment of robust actin stress fibers and focal adhesions. Consistent with these morphological attributes, a quantitative cell adhesion assay revealed that parental A673 cells are less adhesive than those in which EWS-FLI expression was reduced by RNA interference. Knockdown of EWS-FLI in A673 cells is also associated with increased cell motility and loss of anchorage-independent cell growth. Gene expression profiling revealed that expression of EWS-FLI causes downregulation of transcripts encoding several focal adhesion proteins and integrin adhesion receptors by 2-4 fold. By Western immunoblot analysis, we demonstrated that knock-down of EWS/FLI oncoprotein expression in human A673 cells leads to increased expression of focal adhesion constituents such as the actin regulator, zyxin. Introduction of a zyxin expression construct into A673 Ewing's sarcoma cells was sufficient to restore the integrity of the actin cytoskeleton and focal adhesions, and to enhance cell adhesion. In contrast, restoration of zyxin expression in A673 sarcoma cells did not affect cell motility, matrigel invasion, or anchorage-independent cell growth. Thus, oncogenic transformation by EWS-FLI is associated with changes in cytoskeletal architecture, cell adhesion, cell motility/invastion, and cell growth control. Re-expression of a single focal adhesion protein, zyxin, is sufficient to restore cytoskeletal integrity and partially rescue the adhesion deficits seen in A673 sarcoma cells. These studies provide evidence for a zyxin-dependent pathway downstream of EWS-FLI that controls cell morphology and adhesion, as well as zyxin-independent pathways that influence motility/invasion and anchorage-independent cell growth. Loss of adhesion coupled to reduced zyxin expression may be an early step in the establishment of metastatic potential of Ewing's sarcoma 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 5134.
Abstract 5136: Sulfiredoxin promotes cell migration through direct interaction with non muscle myosin IIa
Authors: Bowers Robert , Townsend Danyelle M. , Manevich Yefim , Tew Kenneth D. 
Published: February 2011

Abstract
Redox homeostasis is frequently dysregulated in cancer cells. In particular, glutathione pathways can be imbalanced and impact cell proliferation and death pathways. S-glutathionylation is the addition of glutathione to basic cysteine residues in certain proteins producing significant changes in their structure/function. Because this post-translational modification is dynamic and reversible, the S-glutathionylation cycle can provide the framework for important cell signaling events in cancer cells. We have shown that sulfiredoxin (Srx) plays a role in deglutathionylation and interacts with proteins such as the phosphatase PTP1B, actin and peroxiredoxin 6 (Prdx 6). Redox regulation of actin modulates cell adhesion and focal contacts. In the present study, we examined the role of Srx in cell migration, invasion and potentially metastasis. Srx was over-expressed by transfection in lung cancer cells (A549). Phalloidin staining showed that Srx over-expression (A549-Srx) led to phenotypic changes in cell adhesion through altered focal adhesion contact points and the cells were more refractory to trypsin release. Relative to wild type, A549-Srx cells showed enhanced migration and invasion in the scratch- and Boyden chamber assays. Proteomic analysis through mass spectrometry demonstrated that Srx interacts with non-muscle myosin IIa (NMIIa) in A549 cells. Reciprocal co-immunoprecipitation of Srx and NMIIa validated this interaction under non-stressed conditions. Either through protein: protein interaction or through redox regulation (or both), Srx appears to be an important mediator of the cell motility and invasive properties of the A549 human lung cancer cell line.
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 5136.
Abstract 514: Integrins dependent regulation of endothelial cell migration and tube formation by α6(IV)NC1
Authors: Akulapalli Sudhakar , Boosani Chandra S. 
Published: February 2011

Abstract
Peptides or short protein domains derived from extracellular matrix were shown to possess anti-tumor properties. One such molecule, α6(IV)NC1 was derived from the carboxy terminal non-collagenous domain fragment of α6 chain, type (IV) collagen and was found to inhibit angiogenesis and tumor growth but the mechanism by which it inhibits the growth of solid tumors has not been reported yet. In the present study we demonstrate that the biological functions of α6(IV)NC1 are attributed to its binding to different integrins. In addition, we also demonstrate that α6(IV)NC1 binds to α3β1and α5β1 integrins and competes with the cells binding to α1β1 integrins on type IV collagen, and / with α5β1 integrins on fibronectin and inhibits migration and tube formation of human vascular and lymphatic endothelial cells. We further evaluated the role of α3β1 and α5β1 integrins in tube formation and regulation of cell migration by α6(IV)NC1. While both the integrins (α3β1 and α5β1) are required for the inhibition of tube formation by α6(IV)NC1 in human vascular and lymphatic endothelial cells, only α3β1 integrin was found to regulate lymphatic endothelial cells migration. In addition we also demonstrate that α6(IV)NC1 inhibits tumor growth, tumor lymphatic angiogenesis and circulating endothelial cells in-vivo. These in-vitro and in-vivo findings identify that α3β1 and α5β1 integrins are critical for α6(IV)NC1 mediated inhibition of angiogenic and lymph angiogenic signaling and inhibition of tumor progression. Collectively, our findings first time demonstrate that α6(IV)NC1 is a potent therapeutic candidate for targeting tumor angiogenesis and tumor lymphatic angiogenesis.
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 514.
Abstract 515: Interaction of CD44 with matrix metalloproteinase-9 (MMP-9) is crucial to maintain adhesion, migration and invasion in glioblastoma xenograft cells
Authors: Vanamala Sravan K. , Gondi Christopher S. , Veeravalli Krishna K. , Chetty Chandramu , Fassett Daniel , Klopfenstein Jeffrey D. , Dinh Dzung H. , Gujrati Meena , Rao Jasti S. 
Published: February 2011

Abstract
CD44, a transmembrane receptor for hyaluronic acid, is comprised of an extracellular domain (ECD) and intracellular domain (ICD). CD44 is implicated in various adhesion-dependent cellular processes, including cell migration, tumor cell metastasis and invasion. Here, we have generated constructs for knockdown of CD44 corresponding to ECD and ICD as well as to selectively overexpress either ECD or ICD. CD44 knockdown resulted in a more than 50% reduction in cellular adhesion, migration, and invasion as determined by MTT, wound closure and Matrigel assays in glioblastoma xenograft cell lines (4910 and 5310). Zymography analysis of conditioned medium from CD44 knocked down 4910 and 5310 cells showed decreased gelatinolytic activity of MMP-9; however, western blot analysis of cell lysates did not show any change in MMP-9 expression. Based on these results, we sought to further determine the relationship of CD44 with MMP-9, which is known to play an important role in cellular adhesion, migration and invasion. Immunoprecipitation analysis of cell lysates from 4910 and 5310 cells revealed an interaction between CD44 and MMP-9. Of note, siRNA-mediated knockdown of MMP-9 resulted in inhibition of CD44 cleavage. Selective overexpression of ECD or ICD with downregulation of endogenous CD44 showed that ECD expression was able to recover cellular adhesion and gelatinolytic activity of MMP-9. In contrast, as seen in the MTT assay results, ICD overexpression recovered cell growth but not adhesion or MMP-9 gelatinolytic activity. Taken together, our results suggest the interaction between CD44 and MMP-9 plays an important role in maintaining cellular growth, adhesion, invasion and migration in the glioblastoma xenograft cell lines 4910 and 5310.
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 515.
Abstract 517: Expression of PTRF/cavin-1 in prostate cancer cells reduces migration via decreased MMP9 expression
Authors: Aung Cho S. , Hill Michelle , Parton Robert , PARAT Marie-Odile 
Published: February 2011

Abstract
Caveolin-1 expression and secretion are increased in metastatic prostate cancer and caveolin-1 seems to contribute to prostate cancer growth and metastasis. Caveolin-1 was long believed to be sufficient for caveolae formation, but a cytoplasmic protein named PTRF (Polymerase I and Transcript Release Factor) or cavin-1 was recently found to be required, in concert with caveolin-1, for the formation and functions of caveolae. We hypothesized that PTRF expression could modulate prostate cancer cell migration. In metastatic PC3 prostate cancer cells that express abundant caveolin-1 but no PTRF, heterologous PTRF expression restores caveolae formation and caveolin-1 distribution. We show that PTRF-expressing PC3 cells exhibit decreased migration, and that this effect is mediated by reduced matrix metalloprotease-9 (MMP9) production. We further show that MMP9 production is affected at the transcriptional level, and independently from caveolae formation. Of all the cavin family members, PTRF-cavin-1 is the only one to dramatically reduce MMP9 expression. Taken together, our results suggest that PTRF-cavin-1 expression alters prostate cancer aggressiveness.
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 517.