bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5175: L1 stimulation of human glioma cell motility correlates with FAK activation
Authors: Yang Muhua , Li Yupei , Boulos Magdy I. , Galileo Deni S. 
Published: February 2011

Abstract
Our previous studies showed the expression and proteolysis of neural adhesion molecule L1 (CD171) in human glioma cell lines and human glioma surgical samples. The proteolysis of this molecule was suggested to autocrine stimulate glioma cell motility through binding to integrin receptors (Yang et al., 2009). To further investigate the mechanism of this stimulation, in this study, a lentivirally introduced shRNA was used to attenuate L1 expression in human glioma T98G cells (T98G/shL1 cells), which resulted in 95% decreased expression compared to empty vector infected control cells. L1 attenuated cells exhibited 50% decreased cell motility compared to control cells as shown by time lapse microscopy and the quantitative “Super Scratch” assay. These slower T98G/shL1 cells showed a 68% decrease in FAK activity and an approximately 36% increase in focal complex size compared to control cells. These results suggest that T98G/shL1 cells had decreased focal complex turnover, which resulted in their slower migration. Conditioned media containing the L1 ectodomain was made from CHO cells infected with a lentiviral vector expressing the human L1 ectodomain sequence. Adding L1 conditioned media 1) rescued the cell motility in T98G/shL1 cells and 2) increased cell motility in U118 cells (a grade III human glioma cell line lacking of endogenous L1 expression) by 30% compared to the control cells. These results support a model for stimulation of glioma cell motility through the L1 ectodomain after ADAM10 proteolysis (Yang et al., 2009). In order to examine L1 function in glioma cell invasion into brain tissue, a novel embryonic chick model was used. Injection of GFP labeled T98G cells and dissociated cells from human glioma surgical samples into embryonic chick brains resulted in extensive invasion after 4 days, and this in vivo system is being used to study L1 function in glioma cell invasion. Confocal microscopy of immunostained tissue sections revealed that cell surface L1 was missing in cells located at the margin of the tumor as opposed to cells in the tumor mass. These results are consistent with our previous finding that L1 was expressed on the surfaces of confluent T98G cells in culture, but was lost from the cell surface along the edge of a scratch into which cells migrated. These studies suggest a general mechanism where the L1 ectodomain autocrine stimulates glioma cell motility and invasion by binding to integrin receptors, which activates FAK and thereby increases turnover of focal complexes. Supported by NIH INBRE.
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 5175.
Abstract 519: Differential expression of basement membrane type IV collagen α chains as a prognostic factor of extrahepatic bile duct carcinoma
Authors: Karashima Ryuichi , Hirashima Kotaro , Iyama Ken-ichi , Baba Yoshifumi , Sado Yoshikazu , Ninomiya Yoshifumi , Takamori Hiroshi , Baba Hideo 
Published: February 2011

Abstract
Objective: The destruction of the basement membrane is the first step of cancer cell invasion and metastasis. Type IV collagen is a major component of the basement membrane, and is composed of six genetically distinct α(IV) chains: α1(IV) to α6 (IV). The loss of α5/α6(IV) chains from the epithelial basement membrane at the early stage of cancer cell invasion has been reported in several types of cancers. However, the expression of α5/α6(IV) chains in extrahepatic bile duct carcinoma remains unclear. The expression status of α5/α6(IV) chains in extrahepatic bile duct carcinoma was examined.
Methods: The expression of α(IV) chains, p53, and Ki-67 were examined by using immunohistochemical method in 36 surgical specimens of extrahepatic bile duct carcinoma. The relationship between clinicopathological parameters of 36 patients and the results of immunohistochemical staining was statistically examined using χ2 test or Fisher's exact test. The overall cancer-specific survival was estimated using the Kaplan-Meier method, and the log-rank test was used to evaluate the statistical significance of the differences.
Results: In the normal bile duct mucosa of all examined specimens, both α1/α2(IV) and α5/α6(IV) chains were stained in the basement membrane of the surface columnar epithelium in a continuous linear pattern, while both α3(IV) and α4(IV) chains were not stained. The α1/α2(IV) and α5/α6(IV) chains were also expressed in the basement membrane of smooth muscle cells of the muscularis propria and large blood vessels. In extrahepatic bile duct carcinoma, α5/α6(IV) chains disappeared partially or completely around the tubular cancer cells in 25 of 36 specimens. All of tumors expressed α5/α6(IV) chains were also positive for α1/α2(IV) chains. The expression of α5/α6(IV) chains were significantly correlated to T classification and TNM staging, and inversely correlated to p53 expression. No relationship was observed between the expression of α5/α6(IV) chains and Ki-67 index. The patients with loss of α1/2(IV) and α5/6(IV) chains demonstrated significantly poorer prognosis than those with positive α1/2(IV) chains, irrespective of α5/6(IV) expression.
Conclusion: The loss of α1/2(IV) and α5/α6(IV) chains might be a useful prognostic factor for extrahepatic bile duct 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 519.
Abstract 5192: GEP100 binding to HER2 receptor promotes lung cancer invasion and metastasis
Authors: Toshi Menju , Hashimoto Shigeru , Hashimoto Ari , Date Hiroshi , Sabe Hisataka 
Published: February 2011

Abstract
HER2 overexpression is well known to be a poor prognostic factor in some of epithelial tumors, including breast cancer and lung cancer. Previous reports have shown that GEP100-Arf6-AMAP1 pathway is pivotal for significant population of breast cancer invasion originated from EGFR signaling. Here we have examined the involvement of this pathway in HER2 signal-induced lung cancer invasion and / or metastasis.
Co-immunoprecipitation for the reconstitutive expression of both HER2 and GEP100 or ARNO, the other ArfGEF for Arf6, showed that GEP100, but not ARNO, bound HER2 receptor through its pleckstrin homology (PH) domain. The stimulation of reconstitutively expressed cells with EGF did not increase its binding. On the other hand, the starvation for 24hours decreased. We found that H522 lung adenocarcinoma cells overexpressed HER2 receptor, but less EGFR, compared with the other thoracic cancer cell lines, and that GEP100 endogenously bound HER2, neither EGFR nor HER3 in this cells. In vitro invasion of H522 cells was little promoted with EGF stimulation used as chemoattractants. It suggested that the signal transduction through GEP100 was mainly originated from HER2 signaling in H522 cells, not EGFR.
In vitro invasive activity in H522 cells was decreased by approximately 40-60% with three conditions as follows: the deprivation of HER2 signaling with the selective inhibitor, GEP100 knockdown by siRNA, or the interruption of this binding with the exogenous expression of PH domain of GEP100. And the knockdown of Arf6 and AMAP1, the downstream molecules of GEP100, similarly decreased in vitro invasion.
Immunohistochemical analyses of GEP100 and HER2 expression for 112 cases of resected specimens of human primary lung adenocarcinoma were performed and all samples were scored with the intensity of tumor lesion. These analyses showed that the intensity scores of GEP100 and HER2 were both statistically higher in pN2 cases than in pN1 cases. Furthermore, in cases of very strong HER2 expression (score; 3+), positive expression of GEP100 tended to be correlated with the high frequency of lymphatic metastasis (100% vs 61.5%, p=0.08).
GEP100 binding to HER2 receptor promotes lung cancer invasion and metastasis. Taking account of the importance of GEP100 in invasive mechanisms related with both EGFR and HER2 signaling, this GEP100 molecule appears to be a quite promising target to prevent cancer 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 5192.
Abstract 5196: Granulocyte-colony stimulating factor (G-CSF) plays a causative role for H-Ras-mediated invasion and migration of human breast epithelial cells
Authors: PARK SUN-HWA , MOON AREE 
Published: February 2011

Abstract
The whole human genome microarray on normal MCF10A, N-Ras-transformed, non-invasive MCF10A and H-Ras-transformed invasive MCF10A human breast epithelial cells revealed that the granulocyte-colony stimulating factor (G-CSF) was most highly upregulated in an H-Ras-specific manner. The present study investigated whether G-CSF plays a causative role for H-Ras-mediated MCF10A cell invasion and migration. Importantly, siRNA-mediated knockdown of G-CSF expression significantly reduced H-Ras-induced matrix metalloproteinase(MMP)-2 expression as well as invasion/migration. Activations of Rac1, MKK3/6 and p38 MAPK were inhibited by siRNA-knockdown of G-CSF. The induction of G-CSF expression conferred the invasive/migratory phenotype to parental MCF10A cells. Expression of MMP-2 and activation of signaling molecules Rac1, MKK3/6 and p38 MAPK were increased by G-CSF induction. Taken together, this study revealed G-CSF gene as a candidate marker for metastatic potential of breast epithelial cells.
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 5196.
Abstract 5197: Comparative proteome analysis reveals flotillin-1 as an H-Ras-interacting lipid raft protein critical for breast epithelial cell invasion
Authors: Yong Hae-Young , Hwang Jin-Sun , Kim Myeong-Ok , Sohn Hwa-Jin , Kim Eun-Sook , Choi Wahn Soo , Noh Dong-Young , Hwang Ki-Tae , Kim Hyeong-Reh Choi , Kim Ki-Bum , Lee Jae-Seon , Moon Aree 
Published: February 2011

Abstract
Metastatic spread is the major cause of death from breast cancer. The objective of our study is to unveil signal transduction pathways specific to breast epithelial cell invasion and migration apart from cell proliferation/transformation. We previously showed that the active H-Ras, but not N-Ras, induces invasive/migratory phenotypes of MCF10A human breast epithelial cells via activation of Rac1/p38 signaling leading to MMP-2 up-regulation, while both H-Ras and N-Ras induce cell proliferation and transformation. In the present study, we hypothesized that the Ras isoform-specific signaling pathway is initiated by differential involvement of lipid raft proteins. To address this, we characterized proteome profiles of lipid raft proteins from three cell lines: normal MCF10A; N-Ras-transformed, non-invasive MCF10A; and H-Ras-transformed, invasive MCF10A cells. Among twenty-four lipid raft proteins that were up-regulated in an H-Ras-specific manner, we tested whether flotillin-1 plays a causative role for H-Ras-mediated MCF10A cell invasion/migration. Here, we show that flotillin-1 interacts with H-Ras and H-Ras signaling increases flotillin-1 expression, suggesting a signaling amplification loop between flotillin-1 and H-Ras. Importantly, siRNA-mediated flotillin-1 knockdown significantly reduced H-Ras-mediated motility/invasion accompanied with down-regulation of Rac1/p38 and MMP-2. We also show that flotillin-1 co-localizes with H-Ras in the plasma membrane, while the interaction between flotillin-1 and N-Ras was negligible. Taken together, this study identified flotillin-1 as an H-Ras-interacting lipid raft protein critical for activation of H-Ras-specific signaling resulting invasive phenotype in breast epithelial cells. Consistently, flotillin-1 mRNA was significantly higher in malignant breast cancer tissues, supporting our hypothesis that flotillin-1 may contribute to breast carcinoma invasion.
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 5197.
Abstract 52: Overexpression of uridine phosphorylase 2 (UPP2) in tissues of uridine phosphorylase (UPP1) knock-out mice
Authors: Gao Yang , Ziemba Amy , Turner Jennifer , Pizzorno Giuseppe 
Published: February 2011

Abstract
Uridine phosphorylase (UPase) and thymidine phosphorylase (TPase) play critical roles in the metabolism of pyrimidines and their analogs used in cancer chemotherapy. These enzymes catalyze the reversible conversion of uridine, deoxyuridine and thymidine to the corresponding free bases and ribose or deoxyribose-1-phosphate. Uridine phosphorylase activity, in particular, has been reported to be elevated in breast cancers, colorectal cancer, oral squamous carcinomas, melanoma tissue, and lung adenocarcinomas when compared with adjacent normal tissues. Recently, a novel pyrimidine phosphorylase has been identified, called UPase-2. In human tissues, UPase-2 is predominantly expressed in kidney tissue, while in mouse tissue it is predominately expressed in the liver. Our recent studies have indicated that the UPase-2 isoform is overexpressed in UPase-1 knockout mice we have recently developed. A 37kDa (predicted MW of UPase-2) protein is overrepresented in liver lysate of UPase-/- mice after western blot analysis using a uridine phosphorylase polyclonal antibody. Real time RT-PCR analysis using UPase-2 specific primers shows a 4-fold increase in liver UPase-2 expression in UPase-/- mice compared to wild type mice. We also observed an increase in the expression of this enzyme in kidney and brain tissues; however, the enzymatic activity was below the limit of detection. No detectable mRNA levels were observed in spleen, lung or heart tissues. Interestingly, UPase-2 mRNA expression in wild-type and UPase-/- liver tissue decreased to 32% and 8% respectively after mice were fed diets containing 0.5% fenofibrate for 15 hours, however, UPase-1 mRNA expression increased 3.8-fold in the livers of wild-type mice. Fenofibrate, a ligand for peroxisome proliferator-activated receptor alpha, is used to treat high cholesterol and triglyceride levels, calling into question the role of UPase in lipid metabolism. Both the physiological role of UPase-2 in nucleoside metabolism and the homeostatic regulation of UPase-1 and UPase-2 in liver are presently unclear. To address this question, we plan to study this newly developed animal model to characterize UPase-2 contribution to pyrimidine and fluoropyrimidine metabolism, and the regulatory mechanisms affecting its expression and function.
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 52.
Abstract 521: Impaired migration of human fibrosarcoma cells HT1080 on glycated collagen type I
Authors: Said Georges , Guilbert Marie , Millerot-Serrurot Emilie , Schneider Laurence , Terryn Christine , Garnotel Roselyne , Jeannesson Pierre 
Published: February 2011

Abstract
Although a strict link does exist between cancer and aging, elderly patients present less invasive tumors than their younger counterparts. During aging, the fibrillar collagen type I, which is an abundant component of the extracellular matrix, becomes a prominent target of post-translational modifications such as glycation. Our present study is mainly designed to investigate the effect of non-enzymatic glycation of this long-lived protein on the proliferation and migration of human fibrosarcoma cells HT1080. For this purpose, collagen type I extracted from rat tail tendons was used for in vitro glycoxydation with ribose. Tumor cell behaviour was then evaluated on 2-dimensional plastic surfaces coated with native or glycated collagen type I. Results showed that the proliferation rate of HT1080 cells on glycated collagen type I did not differ from that on native collagen I after 1, 2 and 3 days of culture. Furthermore, the migration ability of HT1080 cells was studied by quantifying cell speed and trajectories via time-lapse videomicroscopy. At day 1, glycated collagen type I distinctly slowed down the cell locomotion by decreasing the mean cell speed by 47% (20.2 μm/h for glycated versus 38.3 μm/h for its native form). Continuous single cell tracking also permitted the investigation of cell trajectories. Cells grown on glycated collagen exhibited shorter or circular trajectories around their starting point in accordance with the cell speed inhibition. Because actin and vinculin appeared as key proteins involved in cell locomotion, we next investigated the effect of glycated collagen on the organization of these proteins in individual cells in motion. Cells exhibited a dramatic disorganization of F-actin cytoskeleton with loss of stress fibers as compared to native collagen. Actin was principally localized at the rim of the cell. Disturbance of actin integrity was accompanied with a disorganization of vinculin that also localized at the cell periphery. The impact of glycated collagen on the non-receptor protein tyrosine kinase FAK, which plays a crucial role in focal adhesion formation and cell locomotion, was also evaluated. We found that at day 1, glycated collagen significantly inhibits FAK expression by 39% but did not affect their phosphorylation state. These data clearly suggest that age-related changes of extracellular matrix proteins may contribute to a less invasive behaviour of tumor cells.
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 521.
Abstract 523: Three-dimensional hyaluronic acid-based hydrogel systems for studies of cancer invasion
Authors: Gurski Lisa A. , Nguyen Ngoc T. , van Golen Kenneth C. , Jia Xinqiao , Farach-Carson Mary C. 
Published: February 2011

Abstract
Currently available invasion assays for study of cancer metastasis have limitations that led us to develop a novel system that provides a more flexible, quantifiable, and physiologically relevant method to study cancer cell invasion. The three-dimensional (3D) hyaluronic acid (HA) hydrogel invasion assay then was used to study HA receptor signaling as it occurs during prostate cancer metastasis to bone marrow. Our invasion assay uses the HA hydrogel which reflects the prevalence of HA in the bone marrow and its key role in the promotion of cancer cell motility and tissue invasion. The HA hydrogel spontaneously crosslinks via interaction of aldehyde and hydrazide groups, allowing for direct encapsulation of cells within the gel. This cell/gel construct is plated in a 12 mm tissue culture insert for construction of the invasion assay. The cells are situated on a single plane so that individual cell movement from that plane can be tracked. We show that our 3D HA hydrogel invasion assay allows for cell migration/invasion in response to a chemoattractant, fetal bovine serum (FBS), and that this movement is easily quantified using confocal microscopy techniques over a distance of up to 1 mm. The ability of cancer cells to invade the HA hydrogel depends on their expression of HA receptors and hyaluronidases; more highly invasive cell lines express HA receptors and hyaluronidases at higher levels. We will show that culture in the HA hydrogel triggers differential expression and/or compartmental translocation of HA receptor proteins and downstream effectors, all of which contribute to motility and metastasis. Ongoing work examines the role that a specific HA receptor, RHAMM, plays in prostate cancer metastasis, specifically how it activates Rho GTPases that increase cell motility. We will show how these physiologically relevant 3-D HA hydrogel invasion assays can be used to study such pathways.
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 523.
Abstract 5232: Phosphatidylethanolamine is a marker of tumor vasculature and can be used as a target for optical imaging
Authors: Stafford Jason H. , Li Shuzhen , Thorpe Philip E. 
Published: February 2011

Abstract
New imaging agents are needed that home rapidly to tumors and saturate their target molecules with the unbound residue then clearing rapidly from the blood stream. Such agents should enable rapid detection of tumors. We have found that a phosphatidylethanolamine-binding peptide known as duramycin is an effective targeting moiety for construction of tumor-specific imaging agents. Phosphatidylethanolamine (PE) is one of two major phospholipids that present in the inner leaflet of the cell membranes, the other being phosphatidylserine (PS). We have previously demonstrated that oxidative stress conditions within the tumor microenvironment cause PS to flip to the outer leaflet in tumor endothelial cells. The exposed PS provides a highly specific marker of tumor vasculature. Since PE and PS distribution within the membrane is co-regulated, we hypothesized that PE would also be a marker of tumor vasculature. To target exposed PE, we generated several biotinylated duramycin constructs. Biotinylated duramycin bound to PE which became exposed on endothelial cells after they had been subjected to oxidative stresses. When the biotinylated duramycin was injected intravenously into mice bearing different types of tumors it rapidly localized to tumor vasculature and did not bind blood vessels in normal tissues. Next, we conjugated duramycin conjugated to a near-infrared fluophore (IRDye 800CW) and used it for optical imaging of subcutaneous RM-1 prostate tumors in mice. The duramycin-targeted near infrared probe efficiently labeled tumors and did not accumulate in non-target tissues giving clear detection of the tumors. These results show that PE exposure, like PS exposure, is a marker of tumor vasculature in many types of cancer. Duramycin labeled with detectable probes may have broad application in cancer imaging.
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 5232.