bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1109: The antimicrobial peptide LL37 activates plasmacytoid dendritic cells in breast cancer
Authors: Vey Nelly , Blanc Elena , Sisirak Vanja , Thys Sandra , Beux Céline Le , Goutagny Nadège , Treilleux Isabelle , Marabelle Aurélien , Blay Jean-Yves , Caux Christophe , Bendriss-Vermare Nathalie 
Published: May 2015

Abstract
Plasmacytoid dendritic cells (pDC) are the main producers of type I IFNs in response to viral and self nucleic acids that trigger endosomal TLR7 and 9. They have been recently described in various solid tumors. In breast tumors, we demonstrated that tumor-associated (TA)pDC exhibit a partially mature phenotype, suggesting that endogenous activating signals are present in tumor microenvironment (TME). Importantly, type I IFN was shown to play a major role in tumor immunosurveillance and we observed a type I IFN signature in human breast tumors. Altogether these observations lead us to investigate whether, in the initiating phase of tumorigenesis, TApDC might be activated by endogenous TLR ligands released in the TME that may trigger their IFN-a production, as observed in auto-immune disorders in response to [self nucleic acids-antimicrobial peptide LL37] complexes. First, we demonstrated that hCAP18/LL37 is expressed by a subset of CD45+ cells within the breast TME. Importantly, [self nucleic acids-LL37] complexes purified from breast TME were able to trigger IFN-a production in healthy pDC in vitro demonstrating their functionality. Finally, using syngenic murine mammary tumor models preliminary data showed that tumor cell growth is accelerated in IFNARko mice and pDC-depleted mice compared to wild-type mice suggesting a role for type I IFN and pDC in controlling early tumor development. Thus, our work aimed at demonstrating that restoring pDCs' immunosurveillance function might represent an attractive therapeutic strategy for localized breast tumors.
Support : Ligue contre le cancer, Fondation ARC (SFI20111203835) and INCA (2011-1-PL BIO-12-IC-1).
Citation Format: Nelly Vey, Elena Blanc, Vanja Sisirak, Sandra Thys, Céline Le Beux, Nadège Goutagny, Isabelle Treilleux, Aurélien Marabelle, Jean-Yves Blay, Christophe Caux, Nathalie Bendriss-Vermare. The antimicrobial peptide LL37 activates plasmacytoid dendritic cells in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1109. doi:10.1158/1538-7445.AM2014-1109
Abstract 1111: Hypoxia inducible factor regulation of galectin3 expression in neuroblastoma cells:Implications in controlling malignant phenotype of neuroblastoma cells
Authors: Wesley Umadevi V. , Resad Esat , Dempsey Robert J. 
Published: May 2015

Abstract
Neuroblastoma (NB) is an extra cranial tumor arising from neural crest progenitor cells. Effective angiogenesis, or new blood vessel formation, is critical for NB tumor growth and progression. Elevated levels of galectin-3 (Gal-3), an angiogenic cytokine is extensively correlated with the malignant behavior and poor prognosis of many cancers. Our studies have shown that Gal-3 expression is significantly up-regulated in aggressive NB cells, and Gal-3 promotes angiogenesis and migration of microglial cells. We have also previously reported that Gal-3 expression is up regulated under low oxygen/hypoxic conditions. The specific mechanisms of Gal-3 induction in NB are not understood. Hypoxic microenvironment drives malignant phenotypes of cancer cells through the transcription factor hypoxia-inducible factor (HIF1). Because NB cells reside in a low oxygen environment, we determined if the hypoxic status modulates Gal-3 expression. In this study, we utilized RT-PCR, western blot analysis, immunofluorescence staining, RNA interference and biochemical approaches. The hypoxia-mimetic, cobalt chloride (CoCl2)-treated neuroblastoma Neuro-2a cells showed enhanced levels of HIF 1 protein. In correlation with the increased HIF1 levels, Gal-3 expression was increased at both RNA and protein levels. Silencing of HIF1 expression by small hairpin interfering RNA in Neuro-2a cells blocked hypoxia induced Gal-3 expression indicating that HIF1 regulates Gal-3 expression in NB cells. Down regulation of Gal-3 resulted in decreased levels of the angiogenic factors IL-6 and urokinase plasminogen activator in association with decreased proliferation, migration, and angiogenesis. Thus our data suggest that HIF1alpha plays a role in the regulation of Gal-3 expression and malignant phenotype of NB cells.
Note: This abstract was not presented at the meeting.
Citation Format: Umadevi V. Wesley, Esat Resad, Robert J. Dempsey. Hypoxia inducible factor regulation of galectin3 expression in neuroblastoma cells:Implications in controlling malignant phenotype of neuroblastoma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1111. doi:10.1158/1538-7445.AM2014-1111
Abstract 1119: Utilization of the TGFβ signaling pathway and cell substrate interaction in a novel anti-cancer drug screen
Authors: Kim Wontak , Hoj Jacob P. , Saguibo Nicholas E. , Fullmer Kendra E. 
Published: May 2015

Abstract
The TGF-β signaling pathway has been demonstrated to play a multifunctional and complicated role in cancer progression, making it an intriguing target for anti-cancer therapeutics. TGF-β signaling drives proliferation of cancer cells, invasion at the tumor periphery, and is associated with metastatic potential in a number of cancer types. Tumors expressing TGF-β activity are positively correlated with poorer prognosis in patients. Complicating the role of TGF-β signaling in cancer progression is that TGF-β signaling leads to distinct cellular responses at different stages of cancer progression. How the same signal transduction pathway drives distinct cellular responses is a critical question. One likely possibility is that TGF-β signaling is highly context dependent. Changes in the tumor microenvironment, as occur during cancer progression, alter the outcome of TGF-β signaling. As an extreme example of how TGF-β signaling is affected by micro-environmental stimuli, we and others previously reported that certain non-cancerous cells on rigid collagen I substrates become sensitized to HGF-induced epithelial scattering in response to TGF-β, while cells on pliant collagen I substrates undergo apoptosis in response to TGF-β. Given that tumors are typically rigid tissues, we sought to define whether cancer cells would respond to TGF-β by undergoing apoptosis when cultured on pliant substrates. We plated a wide variety of cancer cell lines on highly pliant substrates, treated then with TGF-β, and observed cell viability over time. While a number of cells showed no apoptotic response to TGF-β signaling under any condition, we find that a significant number of cancer cells derived from solid tumors respond to TGF-β signaling on pliant substrates by undergoing apoptosis. Another group of cell lines undergo apoptosis on pliant substrates in the absence of any TGF-β stimulation. Reasoning that perturbation of cellular signaling that communicated substrate rigidity to cells might sensitize them to apoptosis in response to TGF-β, we designed a high-content high throughput screen to look for molecules that would induce cells to undergo apoptosis in response to TGF-β signaling. This chemical genetics approach will yield cues into the mechanism of tumor microenvironment sensing, as well as provide lead compounds for development of novel therapeutics
Note: This abstract was not presented at the meeting.
Citation Format: Wontak Kim, Jacob P. Hoj, Nicholas E. Saguibo, Kendra E. Fullmer. Utilization of the TGFβ signaling pathway and cell substrate interaction in a novel anti-cancer drug screen. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1119. doi:10.1158/1538-7445.AM2014-1119
Abstract 1128: Thrombomodulin mediates the migration of cervical cancer cells through the regulation of epithelial-mesenchymal transition biomarkers
Authors: Chang Yu-Jia , Wei Po-Li , Huang Ming-Te 
Published: May 2015

Abstract
Thrombomodulin (TM) has been shown to regulate many physiological and pathological processes, including inflammation, thrombosis, and tumor progression. TM is also a natural anticoagulant that maintains circulatory homeostasis in endothelial cells. However, little is known regarding the role of TM in the progression and metastasis of cervical cancer.
TM-specific RNA interference and a cDNA expression vector were used to manipulate TM expression in cervical cancer cells. Cell growth and cell migration were evaluated using the MTT assay, transwell migration assays, and a biosensor system.
TM silencing did not affect the growth rate of the cells. However, cell migration was dramatically enhanced after silencing of TM in HeLa cells. The overexpression of TM in cervical cancer cells only slightly influenced their proliferative capacity. After overexpression of TM in HeLa cells, their migratory capability was suppressed. Furthermore, we found that the decreased expression of E-cadherin and increase of zeb-1 and snail expression in TM-silenced cells which may be correlated with the results of knocking-down TM increases the migratory ability in this study.
In concludion, our results demonstrate that TM may slightly regulate the growth but played the important role in the migratory ability of cervical cancer cells, suggesting that TM could potentially serve as a novel prognostic and therapeutic target in cervical cancer.
Citation Format: Yu-Jia Chang, Po-Li Wei, Ming-Te Huang. Thrombomodulin mediates the migration of cervical cancer cells through the regulation of epithelial-mesenchymal transition biomarkers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1128. doi:10.1158/1538-7445.AM2014-1128
Abstract 1134: Slug promotes survival during metastasis through suppression of Puma-mediated apoptosis
Authors: Hazan Rachel 
Published: May 2015

Abstract
Tumor cells must overcome apoptosis to survive throughout metastatic dissemination and distal organ colonization. Here we show in the Polyoma Middle T mammary tumor model that N-cadherin causes Slug upregulation, which promotes carcinoma cell survival. Slug was dramatically upregulated in distant metastases relative to primary tumors. Consistent with a role in metastasis, Slug knockdown in metastatic carcinoma cells suppressed pulmonary colonization, due to reducing cell survival, but had no effect on tumor cell invasion or extravasation. In support of a role in cell survival, Slug inhibition by shRNA, sensitized tumor cells to apoptosis by genotoxic stress, resulting in caspase-3 activation and PARP cleavage. Furthermore, the effects of Slug on cell survival were due to direct repression of the pro-apoptotic gene, Puma. Importantly, the survival function of the SLUG-PUMA axis was confirmed in human breast cancer cells, where Slug knockdown increased Puma expression and inhibited lung colonization. Thus, our study demonstrates a pivotal role for Slug in cell survival, which is beyond its role in epithelial-to-mesenchymal transition, implying that disruption of the SLUG-PUMA axis may impinge on the survival of metastatic cancer cells.
Citation Format: Rachel Hazan. Slug promotes survival during metastasis through suppression of Puma-mediated apoptosis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1134. doi:10.1158/1538-7445.AM2014-1134
Abstract 1140: Par-4 mediates EMT in response to TGF-β stimulation
Authors: Fabi François , Chaudhry Parvesh , Singh Mohan , Asselin Eric 
Published: May 2015

Abstract
Endometrial cancer is the most common cancer affecting the female genital tract; this disease also stands as the fourth most frequent cancer affecting occidental women. Endometrial cancer is generally well manageable; however, the high metastatic potential of endometrial tumors represents one of the major hurdles in the treatment of this disease. The epithelial to mesenchymal transition (EMT) has been considered for a long time as a central mechanism by which cancer cells acquire invasive abilities necessary for metastasis formation. Multiple regulatory networks dictate this complex process; however TGF-β has been shown to be one of the most important inductor of EMT in cancer cells. Still, the process by which TGF-β induces this transition has yet to be fully understood. Our study demonstrates that TGF-β upregulates the expression of Par-4, a tumor suppressor protein concomitantly with the onset of EMT. Four uterine cell lines (Hec-1-a, KLE, HeLa, HIESC), one ovarian cell line (SKOV-3) and one breast cell line (MCF7) were used in this study. We first investigated the effect of exogenous TGF-β treatment on these cell lines to determine its effect on Par-4 expression. We've observed that TGF-β increased Par-4 levels in every cell lines. Preliminary analysis determined that this regulation was made through both Smad4 and p65, which was confirmed by the use of siRNA. We've also demonstrated that this regulation was made at the transcriptional level by RT-qPCR. We then sought to confirm the effect of TGF-β on our cell lines and its effect on EMT induction. Our experiments demonstrated that TGF-β promotes EMT as suggested by the upregulation of multiple EMT markers. Transfections using Par-4 expression plasmids induced similar changes, indicating the involvement of Par-4 in TGF-β mediated EMT induction. We then proceeded to assess the effect of Par-4 knockdown concurrent with exogenous TGF-β stimulation. This experiment revealed that Par-4 knockdown reduced the ability of TGF-β to induce Snail expression, further demonstrating the importance of Par-4 in the process of TGF-β mediated EMT. To conclude the study, we sought to understand the effect of XIAP in this process. Our experiments uncovered that XIAP regulates full length Par-4 levels through the inhibition of its caspase-mediated cleavage. Furthermore, the inhibition of XIAP by siRNAs, and thus of Par-4 cleavage, resulted in the reduction of Par-4 EMT inducing capabilities. In conclusion, our study proposes a novel function of Par-4 as an inductor of EMT in multiple cell lines.
Citation Format: François Fabi, Parvesh Chaudhry, Mohan Singh, Eric Asselin. Par-4 mediates EMT in response to TGF-β stimulation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1140. doi:10.1158/1538-7445.AM2014-1140
Abstract 1157: Differential effects of aluminum exposure on epithelial and mesenchymal cells
Authors: AbdelMageed Manar A. , Foltopoulou Parthena , Betancur-Boissel Monica , McNiel Elizabeth A. 
Published: May 2015

Abstract
Introduction: Aluminium [Al(III)] is the third most abundant element as well as the most abundant metal in the Earth's crust. The human population is exposed to Al throughout daily life; in drinking water, food, via application of antiperspirants, use of antacids and vaccination. However, aluminum exposure has been linked to a variety of pathological disorders like anemia, osteomalacia , hepatic disorder, and neurological disorder. In addition, studies report that aluminum levels are higher in tumors, including breast cancers than in surrounding normal tissues. This suggests that aluminum accumulation may provide some selective advantage to the tumor.
Methods/Results:To determine how aluminum affects cells that reside in mammary tissue, we studied the in vitro effects of Al exposure on human mammary epithelial cells and mesenchymal cells. Cells used in our study included hTERT-immortalized human mammary epithelial cells (HMECs), the immortalized human mammary epithelial cell line (MCF10A), hTERT-immortalized reduction mammary fibroblasts (RMF/EG) and a dermal-derived human fibroblast cell line (MSU1.1). Using the MTT assay we found that AlCl3 and AlOH3 salts inhibit the growth of the mammary epithelial cells causing complete inhibition of proliferation at doses around 1mM and decreased proliferation was observed at doses as low as 12.8 uM. Surprisingly at these doses, Al salts caused dose-dependent increase in proliferation the mesenchymal cells. The proliferative effect of Al on mesenchymal cells was confirmed using clonogenic assay. Flow cytometric evaluation of cell cycle using PI/BrdU incorporation demonstrated that in MSU1.1 cells exposed to AlOH3 for 48 hrs, the percentage of cells in S phase of the cell cycle nearly doubled as compared to untreated cells (P &lt;0.05). Similar results were seen with AlCl3 treatment of MSU1.1 and AlOH3/AlCl3 treatment of RMF/EG cells.
Conclusions: These data indicate that while Al salts induce dose dependent cytotoxicity in human epithelial cell lines, they induce proliferation of mesenchymal cells. The tumor microenvironment, including a proliferative stroma, is known to facilitate mammary carcinogenesis. Our data suggest that Al accumulation could promote the development of a permissive microenvironment. We are currently seeking to determine the mechanism for the differential effect of Al in cells and whether this effect influences transformation or carcinogenesis.
Citation Format: Manar A. AbdelMageed, Parthena Foltopoulou, Monica Betancur-Boissel, Elizabeth A. McNiel. Differential effects of aluminum exposure on epithelial and mesenchymal cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1157. doi:10.1158/1538-7445.AM2014-1157
Abstract 1174: VCAM-1 enhances immune evasion in a murine model of metastatic cervical cancer
Authors: Scrimieri Francesca , Bobanga Iuliana Dit , Eid Saada , Corn David J. , Barkauskas Deborah , Myers Jay Jay , Huang Alex Y. 
Published: May 2015

Abstract
Surface over-expression of Vascular Cell Adhesion Molecule-1 (VCAM-1) has recently been identified as a mechanism used by metastatic breast cancer cells to provide pro-survival advantages. It has been previously shown that the metastatic and immune-resistant mouse cervical cancer cell line, A17 has a significantly increased expression of VCAM-1 compared with the primary parental tumor cell line, TC1-P0. Using this metastatic tumor model, we first modulated the surface expression levels of VCAM-1 on A17 in vitro by using an shRNA knockdown approach. We then inoculated these cells intra-venously (iv) and subcutaneously (sq) into C57BL/6 background mice and athymic nude mice to interrogate how VCAM-1 expression affects surrounding immune cell interactions within the tumor microenvironment. To further characterize VCAM-1 dependent immune responses, we used intravital 2-photon laser-scanning microscopy (2P-LPS) to dynamically visualize immune-tumor cells interaction. We observed that VCAM-1 down-regulation reduces the primary tumor growth kinetics in C57BL/6 mice but exhibited similar growth kinetics in nude mice, suggesting that VCAM-1 levels are not responsible for the intrinsic primary tumor growth differences in vivo. Moreover, VCAM-1 down-regulated cell lines showed decreased lung metastasis in both immune-competent mice and athymic nude mice. Furthermore, the metastatic lung parenchyma in mice injected with the non-silencing shVCAM-1 control exhibited immune cell infiltrates with a predominance of M2 polarized macrophages and an altered cytokine production. This may be responsible for decreased susceptibility to immune surveillance. Together, our results demonstrate that tumor-associated VCAM-1 expression helps aggressive tumors circumvent effective immune surveillance, and may represent a target for the development of immune-mediated therapy in metastatic cervical cancer.
Citation Format: Francesca Scrimieri, Iuliana Dit Bobanga, Saada Eid, David J. Corn, Deborah Barkauskas, Jay Jay Myers, Alex Y. Huang. VCAM-1 enhances immune evasion in a murine model of metastatic cervical cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1174. doi:10.1158/1538-7445.AM2014-1174
Abstract 1176: Tumor derived peptide from a2 isoform of Vacuolar ATPase immunomodulates tumor associated neutrophils
Authors: Ibrahim Safaa A. , Amin Magdy , Beaman kenneth D. 
Published: May 2015

Abstract
It has been recently discovered that tumor associated neutrophils (TAN) develop N2 polarization similar to tumor associated macrophages (TAM). It is believed that the tumor microenvironment can provoke the wound repair response from TAN and TAM which in turn promotes tumor progression. Transforming growth factor- β (TGF-β) plays a key role in N2 polarization, however, other regulatory mechanisms are still unclear. a2 isoform Vacuolar ATPase (a2V) are highly expressed on tumors and macrophages. Recent evidence showed that a cleaved peptide from the N-terminal domain of a2V (a2NTD) is secreted in the microvesicles collected from various tumor cell lines. This peptide promotes the pro-tumorigenic characteristics in macrophages. Moreover, priming neutrophils with tumor conditioned media (TCM) collected from breast cancer cell lines promotes the pro-tumorigenic properties in neutrophils. In this study, we are evaluating the in vitro immune-modulatory effect of a2NTD on polymorphnuclear leukocytes (PMN) in order to explore the role of the a2V in the sterile inflammation associated with tumor progression. We isolated PMN from heparin anti-coagulated blood collected from healthy adult volunteers. TCM were collected from MDA-MB-231 breast cancer cell line. PMN were stimulated with either recombinant a2NTD or with TCM to simulate the tumor microenvironment. In both a2NTD and TCM cultures, distinctive morphological changes were revealed by microscopical examination and significant elevation of ROS levels were detected by flow cytometry (p-value &lt;0.05). Moreover, we have observed an upregulation in PMN gene expression of CCL2, CXCL-1, CXCL-2, TNFα, VEGF, MMP-9, neutrophil elastase as well as a2V when it is cultured with either a2NTD or TCM using quantitative real time PCR. In accordance with Queen M., et al, flow cytometry showed delayed PMN apoptosis in cultures with TCM while upon inhibiting V-ATPase, PMN survival decreased significantly (p-value &lt;0.05).This suggests that the delayed apoptosis observed in TCM primed PMN is mediated at least partially by V-ATPase. In addition, a2NTD increased significantly the PMN survival but to a lesser extent compared with TCM. Interestingly, we observed significant surface over-expression of a2V on PMN in both cultures using flow cytometry (p-value &lt;0.05) and confocal microscopy. Our study demonstrates the potential immune-modulatory effect of tumor associated a2NTD on PMN which may indicate its involvement in tumor progression.
Citation Format: Safaa A. Ibrahim, Magdy Amin, kenneth D. Beaman. Tumor derived peptide from a2 isoform of Vacuolar ATPase immunomodulates tumor associated neutrophils. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1176. doi:10.1158/1538-7445.AM2014-1176