bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5272: Endothelin-1 enhances cell migration in human chondrosarcoma cells through PI3K signaling pathways
Authors: Wu Min Huan , Tang Chih-Hsin , Huang Chih-Yang , Lin Tzu En 
Published: February 2011

Abstract
Tumor malignancy is associated with several features such as proliferation ability and frequency of metastasis. Endothelin-1 (ET-1), the most potent vasoconstrictor, and plays a crucial role in the migration and metastasis of human cancer cells. We found that treatment of human chondrosarcoma cells (JJ012 cells) with ET-1 increased migration activity and the expression of matrix metalloproteinase (MMP)-13. Pretreatment of cells with phosphatidylinositol 3-kinase (PI3K), AKT and mammalian Target of Rapamycin (mTOR) inhibitor reduced ET-1- mediated cell migration and MMP-13 expression. In addition, NF-kappaB inhibitor (PDTC) or IkappaB protease inhibitor (TPCK) also inhibited ET-1 -mediated cell migration and MMP-13 up-regulation. Stimulation of cell with ET-1 induced PI3K, AKT and mTOR phosphorylation. Furthermore, the ET-1-mediated increasing kappaB-luciferase activity was inhibited by the specific inhibitor of PI3K, Akt and NF-kB cascades. Taken together, these results suggest that the ET-1 activate PI3K/AKT/mTOR, which in turn activates IKKalpha/beta and NF-kappaB, resulting in the activations of MMP-13 and contributing the migration of human chondrosarcoma 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 5272.
Abstract 5276: CXCL7/CXCR2 axis and invasion
Authors: Yu Minghuan , Kosir Mary A. 
Published: February 2011

Abstract
Introduction: The CXCL7/CXCR2 axis interfaces with matrix molecules whereby the chemokine CXCL7 binds heparan sulfate and the G-protein-linked receptor CXCR2. CXCL7-transfected breast cells acquire the ability to invade through Matrigel. The purpose of this study was to test the effect of inhibition of heparan sulfate binding and CXCR2 binding on invasion.
Methods: Stably transfected breast cells (MCF10AT) were tested with CXCL7-siRNA, and a specific CXCR2 antagonist (SB225002). Inhibition was verified by real time PCR and heparanase ELISA assay. Matrigel invasion assays were performed.
Results: SB225002 and CXCL7 siRNA blocked invasion through Matrigel as compared to controls (p&lt;0.01), and CXCL7 siRNA significantly decreased heparanase activity (p&lt;0.01).
Conclusion: Interfering with either heparan sulfate binding by CXCL7 or its binding to CXCR2 leads to decreased invasion through Matrigel.
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 5276.
Abstract 5277: S100A7 modulates EGFR signaling in estrogen receptor negative breast cancer cell lines
Authors: Qamri Zahida , Nasser Mohd W. , Abdussamad Abdalla , Lill Nancy , Ganju Ramesh K. 
Published: February 2011

Abstract
Purpose of Study: S100A7 (psoriasin) is highly expressed in estrogen receptor alpha negative (ER-α−) and EGFR+ basal like phenotype, especially triple negative, that have been associated with worse prognosis and outcome. However, not much is known about the role of S100A7 in promoting tumorigenesis of ER-α− and EGFR+ breast cancers. We hypothesize that S100A7 secreted by tumor cells may modulate tumor growth by binding to receptor for advanced glycation end-products (RAGE) and activating EGFR in ER-α−. In the present study, we analyzed recombinant S100A7-mediated EGFR signaling that enhances breast tumorigenesis and metastasis in ER-α− cells.
Methods: We examined the effect of recombinant S100A7 on cell migration and motility of ER-α− MDA-MB231 and MDA-MB453 breast cancer cell lines. In addition, we analyzed S100A7-mediated signaling mechanisms by monitoring changes in phosphorylation and expression of various signaling molecules by Western blot, immunoprecipitation and immunofluorescence. We also co-transfected HEK-293 with EGFR and RAGE plasmids to analyze crosstalk between S100A7/RAGE and EGF/EGFR in these cells.
Results: We observed high expression of RAGE in ER-α− MB-231 and MB-453 breast cancer cell lines by FACS analysis. We have also shown that S100A7 is secreted in the conditioned media of ER-α− MB-231 overexpressing S100A7 cells. Recombinant soluble S100A7 was shown to induce cell migration and wound healing in MB-231 and MB-453 cells. These effects were mediated through RAGE, as RAGE neutralizing antibody blocked S100A7-mediated functional effects. To further analyze the molecular mechanism of S100A7-mediated signaling, we observed that recombinant S100A7 transactivates EGFR. Further analysis of molecular mechanism revealed that S100A7 enhances AKT and Erk phosphorylation as well as increases association between Jab-1 and EGFR. The crosstalk between S100A7/RAGE and EGF/EGFR was further confirmed by co-transfecting HEK-293 cells with EGFR and RAGE. Recombinant S100A7 was shown to induce EGFR phosphorylation in these transfected cells, confirming S100A7 may transactivate EGFR by binding to RAGE. Conclusion: These studies reveal that S100A7 may enhance metastatic potential of ER-α− cells by binding to RAGE and activating EGFR signaling. Furthermore, these studies may help in the development of S100A7/RAGE as novel therapies target for ER-α− breast cancer, especially triple-negative and EGFR+ basal-like cancers, which are highly aggressive and difficult to treat.
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 5277.
Abstract 5278: Inhibition of tumor cell migration and metastasis by the GPR4 receptor
Authors: Castellone Reid D. , Leffler Nancy R. , Yang Li V. 
Published: February 2011

Abstract
GPR4, a G protein-coupled receptor, has been shown to function as a proton sensor. Within tumor microenvironments, the interstitial acidic pH may activate GPR4 to regulate the behavior of tumor cells, blood vessels, and other cells. The expression of GPR4 is detected in some tumor cells, and it is the focus of this study to investigate the effects of acidosis/GPR4 signaling on tumor cell migration and metastasis. B16F10 melanoma cells and TRAMP-C1 prostate cancer cells, genetically engineered to overexpress GPR4 or the control vector, were subject to a series of cell motility assays. Transwell and wound closure assays were performed to examine cell migration, and it was observed that upon GPR4 activation in an acidic pH, cell migration was inhibited two to four fold in comparison to the vector control. These same trends were observed for invasion assays, in which Matrigel or a HUVEC endothelial monolayer was applied to the top of each transwell filter. To elucidate the molecular mechanism by which acidosis/GPR4 mediated motility inhibition occurs, G-LISA RhoA activation assays were used and it was observed that upon GPR4 activation in an acidic environment, the levels of activated RhoA, when compared to the vector control, were increased two and three fold. Furthermore, activation of Rho by its activator CN01 in B16F10 and TRAMP-C1 tumor cells recapitulated the acidosis/GPR4 induced motility inhibition phenotype, while inhibition of Rho reversed such phenotype. To examine the biological effects in vivo, B16F10 cells were injected into C57BL/6 female mice through tail veins. Pulmonary melanoma metastasis was inhibited by greater than 80% in GPR4 overexpressing B16F10 cells in comparison to the vector control. Upon treatment with the Rho activator CN01 in culture, the phenotype of the B16F10 vector cells paralleled that of the GPR4 overexpressing cells as metastasis was inhibited by more than 90%. These findings suggest that GPR4 activation by acidic pH plays a role in the inhibition of migration and invasion in B16F10 and TRAMP-C1 tumor cells, and the activation of Rho is at least partly responsible for this phenotype on the molecular level.
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 5278.
Abstract 5279: LPS-TLR4 binding increases metastatic potential of colorectal cancer cells
Authors: Hsu Rich YC , Chan Carlos HF , Spicer Jonathan D. , Rousseau Mathieu C. , Perera Rushika , Giannias Betty , Rousseau Simon , Ferri Lorenzo E. 
Published: February 2011

Abstract
Objective: Infectious complications in colorectal cancer patients undergoing curative resection are associated with cancer recurrence, but the exact mechanism is not well understood. Toll-like receptor 4 (TLR4) is the sole receptor for lipopolysaccharide (LPS), a gram-negative bacterial antigen involved in such infectious complication. TLR4 expression has been found on several cancer types. We hypothesize that LPS promotes cancer cell metastatic potential via TLR4 signaling in colorectal cancer cells.
Methods: We compared the effects of LPS stimulation on two well-characterized colorectal cancer cell lines: Caco-2 (non-metastatic) and HT-29 (metastatic). Flow cytometry was performed to detect cell surface TLR4 and various integrin expression. Cancer cells were incubated with or without 0.1 µg/mL LPS for 4 hours. In vitro static adhesion assay was used to study the ability of cell adhesion to extracellular matrix proteins (fibronectin, collagen I and collagen IV). Intravital microscopy, a technique used to study microcirculation in vivo, was carried out to observe dynamic attachment of intra-splenic injected cancer cells to C57/BL6 mouse liver sinusoids.
Results: Caco-2 cells lack TLR4 receptors and are unresponsive to LPS treatment. In contrast, HT-29 cells were shown to express TLR4 receptors and HT-29 responds to LPS by a 2-fold increase of β1, but not α5, integrin expression in LPS-treated HT-29 cells (Mean Fluorescence Intensity:1041 vs. 458(untreated)). LPS-treated HT-29 cells showed enhanced attachment to fibronectin (1.6-fold; p &lt; 0.01), collagen I (3-fold; p &lt; 0.01) and collagen IV (2-fold; P &lt; 0.01) relative to controls in vitro. Similarly, adherence of HT-29 cells to hepatic sinusoids in vivo was increased by LPS treatment (2 fold; p &lt; 0.05).
Conclusion: These data suggest that LPS-TLR4 signaling in colorectal cancer cells increases the metastatic potential. LPS-TLR4 mediated signaling cascade may be a valuable therapeutic target for the prevention of cancer 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 5279.
Abstract 5282: TRPM7, a novel regulator of human nasopharyngeal carcinoma cells Ca2+ influx and migration
Authors: Chen Jian-Peng , Luo Rong-Cheng , Li Rong , You Chang-Xuan 
Published: February 2011

Abstract
Ion channels are involved in various physiologic and pathologic processes, including the migration of tumor cells that is required for metastasis. To determine whether transient receptor potential melastatin 7 (TRPM7) Ca2+ channels play an important role in the migration of tumor cells, we examined the potential function of TRPM7 channels in the migration of 5-8F human nasopharyngeal carcinoma cells. The migratory potential of the cells was impaired by TRPM7 inhibitors (La3+, 2-APB), and their migration was reduced significantly after either TRPM7 was silenced or extracellular Ca2+ was removed. Conversely, addition of TRPM7 activator (BK) promoted the migration of 5-8F cells. Furthermore, the Ca2+ influx regulated by TRPM7 activated release of Ca2+ stores by a calcium-induced calcium release mechanism. This study suggests, first, that Ca2+ influx is required for the migration of human nasopharyngeal carcinoma 5-8F cells. Second, and more importantly, it identifies TRPM7 as a novel potential-regulator of the Ca2+ influx that allows migration of 5-8F cells. TRPM7, therefore, might have potential as a prognostic indicator and as a therapeutic target in cancer.
Keywords: TRPM7; nasopharyngeal carcinoma cells; 5-8F; Ca2+ influx; Ca2+; migration.
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 5282.
Abstract 5284: The Oncogenic Role of MALL in NSCLC
Authors: Lai Yen-Chun 
Published: February 2011

Abstract
MALL (T-cell differentiation protein-like) located on the human chromosome 2q13 locus encodes a 17.5KDa protein enriched in glycolipid and cholesterol enriched membrane raft (GEM). It is involved in the raft-mediated trafficking machinery in endothelial cells. Previous study showed that MALL can interact with Caveolin-1. However, Caveolin-1 can be phosphorylated by FAK and then promotes cell proliferation and colony formation in NSCLC (non-small cell lung cancer) cell lines. However, the role of MALL in cancer progression is totally unknown. In this study, we found that the expression of MALL is upregulated up to 250-fold in the high invasive lung cancer cells (CL1-5) than low invasive cells (CL1-0). To investigate the biological function of MALL, we first generated a constitutively MALL-expressed lung cancer cell line. We found that MALL can significantly enhance cancer invasiveness by the Boyden chamber matrigel assay (2.12 fold, p&lt;0.01). MALL also promote cell migration by the transwell assay (1.53 fold, p&lt;0.01) and wound healing assay. Moreover, MALL increased the colonogenesis of lung cancer cells by using an anchorage-dependent colony formation assay (1.73 fold, p=0.035) but did not affect the rate of cell proliferation by MTT assay. These findings indicated that MALL can promote tumor metastasis and tumorigenesis. To determine the underlying mechanisms by which MALL increases tumorigenesis and invasion Affymetrix oligonucleotide analysis was performed. The genes differentially expressed between MALL and mock transfectants with greater than two-fold change was identified by ANOVA analysis (FDR&lt; 0.05). The most relevant networks involved were analyzed using MetaCore and IPA (ingenuity pathway analysis) software including cytoskeleton, ECM signaling, and other networks. Taken together, MALL may be a potential oncogene which might provide new insights into the future treatment of lung cancer.
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 5284.
Abstract 5285: PERK regulates autophagy and survival of luminal cells during mammary acinar morphogenesis
Authors: Avivar-Valderas Alvaro 
Published: February 2011

Abstract
During normal mammary gland development both alveoli and lactiferous ducts develop a hollow lumen. Integrin-mediated cell attachment to the extracellular matrix (ECM) is crucial for proper growth and survival of mammary epithelial cells. Improper engagement to the surrounding ECM lead to the adhesion-dependent programmed cell death, or anoikis. However, in early breast cancer these hollow ducts become filled with anoikis-resistant cells, a hallmark of ductal carcinoma in situ (DCIS). The endoplasmic reticulum (ER) kinase PERK is a critical mediator of the translational repression during ER stress and is activated in matrix-deprived cells. Novel findings showed that ECM detachment robustly induces autophagy which transiently promote survival of luminal cells. Autophagy is a tightly regulated anabolic pro-survival process but if not reversed can ultimately lead to cell death. ER stress signaling and in particular PERK can activate autophagy. Furthermore, autophagy has been proposed as a mechanism to enhance the survival of early transformed cells lacking proper ECM contact. Using constitutive inhibition of PERK, we previously found that in ECM bound cells this kinase has an anti-proliferative function. However, this strategy precluded us from testing the precise regulation of PERK during lumen formation. Using MCF10A-Fv2E-PERK cells, where PERK phosphorylation is induced by the divalent molecule AP20187 (AP), we have now found that PERK promotes survival of intraluminal cells via autophagy. During mammary acinar morphogenesis PERK phosphorylation becomes detectable by day 4, peaks at day 6 and after day 8 it is extinguished. This coincided with the timing of autophagy induction in luminal cells. AP-mediated activation of PERK in Fv2E-PERK 3D cultures beyond day 8, induced ATG7 and Beclin1 expression, suggesting that accumulation of luminal cells is linked to autophagy. PERK induction of autophagy might block apoptosis because AP treatment resulted in a downregulation of BimEL expression and an overall reduction in the percentage of apoptotic cells. Moreover, mechanistic analysis revealed that PERK induction of autophagy is dependent on mTOR-&gt;p70S6K signaling inhibition. We propose that PERK mediated inhibition of mTOR protects basement membrane detached cells from apoptosis via autophagy allowing for proper morphogenesis. We conclude that PERK activation in luminal cells leads to increased survival and luminal cell accumulation. This is associated with increased autophagy gene expression/processing and reduced expression of the pro-apoptotic factor BimEL.
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 5285.
Abstract 5288: S100PBP is ubiquitously expressed and modulates the function of S100 calcium-binding proteins in pancreatic cancer
Authors: Lines Kate E. , Audi Namaa , Chelala Claude , Kocher Hemant , Wijesuriya Nilu , Hurst Helen , Crnogorac-Jurcevic Tatjana 
Published: February 2011

Abstract
We have recently discovered a 37kDa novel S100P-binding protein, S100PBP, which shows no homology to any currently known protein; we have therefore explored its expression in a wide range of normal and cancer tissues, its cellular localization and performed several in vitro functional assays to define its putative roles.
In order to determine S100PBP localization in human samples immunohistochemistry was performed on a multi-organ tissue array (Pantomics) and on an in-house made pancreatic ductal adenocarcinoma tissue array including normal, cancer and metastatic lesions. To determine S100PBP function cells with both silenced and stably over-expressing S100PBP were established and investigated by Affymetrix gene expression arrays and a battery of functional assays including adhesion, migration and invasion.
We show that this protein is almost ubiquitously expressed, in varying levels, between normal and tumor specimens, which is both cancer- and tissue-type dependent. In normal pancreas it is widely expressed in both exocrine and endocrine compartments while in pancreatic adenocarcinoma its expression is absent in the stroma and retained in some of the cancer cells but with significantly lower intensity.
We further show that in addition to S100P, in pancreatic cancer cells S100PBP binds, in a calcium-dependant fashion, several other S100 proteins, namely S100A2, S100A4 and S100A6. Over-expression of S100PBP led to changes in the expression levels of S100P and S100A9, which were down-regulated, and S100A4, which was up-regulated. Furthermore, manipulation of S100PBP expression led to phenotypic changes affecting the adhesive, migratory and invasive capacity of pancreatic cancer cells, that varied depending on the cellular context and constellation of the different S100 proteins present. Both over-expression and silencing of S100PBP also led to an increase/decrease in Cathepsin Z levels, respectively.
In summary, S100PBP is ubiquitously expressed and is deregulated in many different cancer types, and appears to play a role in the adhesive, migratory and invasive capabilities of pancreatic cancer 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 5288.
Abstract 5289: HO-3867 inhibits cell migration, invasion and tumor growth of ovarian cancer through alterations in fatty acid synthase (FASN) and focal adhesion kinase (FAK) signaling
Authors: Selvendiran Karuppaiyah , Ahmed S. , Dayton A. , Bratasz A. , Kuppusamy ML. , Rivera BK. , Kuppusamy K. Hideg and P. 
Published: February 2011

Abstract
Fatty acid synthase (FAS) has been found to be overexpressed in a wide range of epithelial tumors, including ovarian cancer. Expression of FAS, the key enzyme in de novo synthesis of long-chain fatty acids, is normally low but increases in cancer. The increase of FAS levels regulates cell proliferation, apoptosis and migration in tumors. In tumor cells, the inhibition of FAS elicits cell cycle arrest and apoptosis, so it is considered a potential drug target for cancer therapy. A2780 and SKOV3 ovarian cancer cells were grown in vitro and exposed to culture media containing 10 μM of HO-3867 for a period of 12 or 24 hours. FAS protein level analysis and examination of proliferation and migration genes was performed by Western blotting. RT-PCR was used to examine mRNA levels. FAS activity levels were measured by spectrophotometry. FAS, Cyclin D1 and VEGF expression levels were analyzed in vivo using both Western blotting, RT-PCR and immunohistochemistry. We found that HO-3867 significantly inhibits the FAS activity levels in A2780 and SKOV3 ovarian cancer cells. FAS mRNA levels were significantly decreased in HO-3867-treated cells. Based upon these results, we investigated how HO-3867 inhibits FAS expression and activity in ovarian cancer cells. We found that FAS-regulating genes such as SREBP1 & 2 and pHER1 were clearly inhibited by HO-3867 exposure. Collectively, our results indicate that HO-3867 inhibition of FAS leads to inhibition of the cell migration genes FAK, ERK1/2, c-Myc, upregulation of the proliferation-regulating genes p21, p27 and downregulation of cyclin D1, resulting in inhibition of ovarian cancer cell proliferation, migration and tumor 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 5289.