bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5171: EpCAM expression governs tumor growth or distant metastasis of human endometrial cancer: grow or go theory
Authors: Wen Kuo-Chang , Wang Peng-Hui , Sung Pi-Lin , Lee Mong-Hong , Wu Cheng-Wen 
Published: August 2015

Abstract
Endometrial cancer is the most common gynecologic malignancy in United States. The prognosis is generally better because most patients are diagnosed at early stage. However, the overall survival rate declines to 10∼20% at advanced stage. There are no effective treatment in the management of patient with late stage of endometrial cancer or distant metastasis. EpCAM (also called TACSTD1 or CD326), a transmembrane glycoprotein, can mediate cell-cell adhesion. Its overexpression negatively correlates with clinical survival in gallbladder cancer, ampullary carcinoma, and squamous cell carcinoma of head &. neck. However, a controversial role of EpCAM is reported in Lynch syndrome and rectal cancer as a tumor suppressor gene. To study the role of EpCAM in endometrial cancer, we manipulate the EpCAM expression in loss-of-function experiment in vitro; the results demonstrate that decrease of EpCAM expression is significantly related to increase invasion ability and diminish cell proliferation. These finding can be reversed after gain-of-function in EpCAM knock-down endometrial cancer cells. EpCAM knock-down is indeed linked to the cell signaling pathway of proliferation (regulation of cell proliferation GO:0042127, regulation of cell death:GO:0010941, regulation of apoptosis: GO:0042981) and migration (biological adhesion:GO:0022610, cell adhesion:GO:0007155, cell migration:GO:0016477) from microarray analysis. Significant more number of lymph node metastasis can be found in vivo at mice with IUI (intra-uterine injection) of EpCAM knock-down cells; moreover, smaller tumor size is observed in subcutaneously injected mice. Among the patients with endometrial cancer, the clinicopathologic characteristics, such as stage, lymph node metastasis, CA-125 value, and overall survival, are significantly related to the low EpCAM expression. Conclusively, diminishing EpCAM can promote endometrial cancer invasion; furthermore, the EpCAM expression is an significant prognostic factor in human endometrial cancer. These data has important implication that development targeting EpCAM in the treatment of endometrial cancer is the new application in future.
Citation Format: Kuo-Chang Wen, Peng-Hui Wang, Pi-Lin Sung, Mong-Hong Lee, Cheng-Wen Wu. EpCAM expression governs tumor growth or distant metastasis of human endometrial cancer: grow or go theory. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5171. doi:10.1158/1538-7445.AM2015-5171
Abstract 5198: Contribution of inflammatory cytokines to CD44-mediated breast cancer metastatic potential
Authors: Covert Hunter , Mellor Liliana 
Published: August 2015

Abstract
The purpose of this study was to elucidate the relationship between the inflammatory cytokine oncostatin M (OSM) and cell migration-promoting CD44 in breast cancer metastasis. OSM-induced CD44 expression was studied in multiple human breast cancer cell lines, including triple negative (TNBC) MDA-MB-231 and estrogen receptor/progesterone receptor-positive (ER+/PR+) T47D and MCF-7 cells. Western blot analysis and RT-PCR demonstrated that OSM is capable of upregulating the expression of the standard form of CD44 (CD44s), as well as inducing multiple CD44 variants produced by alternative splicing. Confocal microscopy was performed and displayed highly organized CD44 around the edge of the cell after OSM treatment. OSM treatment also increased the breast cancer stem cell (BCSC) population (CD44+/CD24−), as measured by flow cytometry. To examine the importance of OSM-induced CD44 in tumor cell migration, we conducted migration assays with and without siCD44 and treatment with OSM. These results verified that OSM-induced CD44 is important for cellular migration. In conclusion, our studies demonstrate that OSM increases the expression of CD44s and its variants, as well as induce a BCSC phenotype. Furthermore, we show that OSM-induced CD44 plays a role in migration, which is an essential characteristic of breast cancer metastasis.
Citation Format: Hunter Covert, Liliana Mellor. Contribution of inflammatory cytokines to CD44-mediated breast cancer metastatic potential. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5198. doi:10.1158/1538-7445.AM2015-5198
Abstract 5205: Docosahexaenoic acid (DHA) alters breast cancer exosome-mediated microRNA signaling
Authors: Hannafon Bethany N. , Carpenter Karla , Berry William , Janknecht Ralf , Dooley William , Ding Wei-Qun 
Published: August 2015

Abstract
DHA is a long-chain omega-3 polyunsaturated fatty acid that has anticancer properties, including the ability to suppress tumor angiogenesis. However, the precise mechanism of DHAs anti-angiogenic activity is not well defined. It is recognized that the intercommunication between cancer cells and their microenvironment is essential to tumor angiogenesis. Exosomes are nanometer-sized extracellular vesicles that are important mediators of intercellular communication and in recent years, the role of tumor-derived exosomes in cancer progression has been realized. However, ways to limit or alter their influence on cancer progression has not been demonstrated. At this time, very little is known about the role of breast cancer derived exosomes in contributing to breast cancer progression and whether these exosomes mediate DHAs anticancer activity. To investigate, breast cancer exosomes were collected from the conditioned media of MCF7 and MDA-MB-231 breast cancer cells engineered to express GFP-tagged CD63 after treatment with DHA. We observed an increase in exosome secretion from the DHA-treated cells. Total RNA was extracted from the DHA-treated and control MCF7-derived exosomes and analyzed by small RNA sequencing. The expression of 83 exosome microRNAs was altered by DHA (&gt;2-fold) and several of the most abundant exosomal microRNAs (miR-23b, miR-27a/b, miR-21, and miR-320b) are known to have anti-angiogenic activity. When DHA-treated MCF7 cells were co-cultured with or the collected exosomes were directly applied to endothelial cell cultures, we observed an increase in the expression of these microRNAs in endothelial cells. Furthermore, overexpression of miR-23b and miR-320b in endothelial cells decreased the expression of their pro-angiogenic target genes (PLAU, AMOTL1, NRP1 and ETS2) and significantly inhibited tube formation by endothelial cells, an effect that could be reversed by inhibition of exosome secretion via Rab27A knockdown. These results suggest that the microRNAs transferred by exosomes mediate DHAs anti-angiogenic action. Our data demonstrates that DHA alters breast cancer exosome secretion and microRNA contents that leads to the inhibition of endothelial tube formation. These results provide insight into the future possibility of developing new cancer therapeutic strategies targeting exosome secretion and content transmission.
Citation Format: Bethany N. Hannafon, Karla Carpenter, William Berry, Ralf Janknecht, William Dooley, Wei-Qun Ding. Docosahexaenoic acid (DHA) alters breast cancer exosome-mediated microRNA signaling. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5205. doi:10.1158/1538-7445.AM2015-5205
Abstract 5208: Neovascularization in brain metastasis is through both angiogenesis and vasculogenesis
Authors: Mok Stephanie , Ang Lee-Cyn , Howlett Christopher J. , Khan Zia A. 
Published: August 2015

Abstract
Metastatic brain tumors are the most common brain tumor in adults with an incidence 10 times greater than primary brain tumors. A variety of malignancies eventually spread to the brain, with a majority arising from cancers of the lung, breast, kidney, and skin. Experimental studies using breast and melanoma cell lines have recently shown that growth of metastatic brain tumors may occur by utilizing pre-existing blood vessel, or by co-opting rather than inducing new vessel formation. Whether the same mechanisms of vascular utilization and expansion play a role in human metastatic brain tumors is unknown and is the focus of the present study.
We examined the immuno-phenotype of blood vessels in primary and metastatic human brain tumors to determine the presence of new blood vessels formation. Glioblastoma multiforme (n = 12) and secondary tumors from melanoma (n = 10), breast (n = 10), kidney (n = 5), and lung (n = 13) all showed extensive immunoreactivity for endothelial marker CD31. We also found a significant number of endothelial cells expressing Ki-67, most notably among breast carcinoma, glioblastoma multiforme and melanoma cases, indicating microvessel proliferation and angiogenesis. Interestingly, both primary and secondary metastatic tumors also showed vascular endothelial cells concomitantly expressing stem cell markers, such as Oct4, suggesting that some of these microvessels are derived through vasculogenesis. These findings show that both proliferation of endothelial cells and de novo endothelial differentiation may underlie metastatic tumor growth to different degrees depending on their site of primary origin. Currently, our laboratory is determining the exact contribution of angiogenesis and vasculogenesis in brain metastasis.
Our findings show that neo-vessels are evident in brain metastasis. Elucidating the source of these vessels may uncover new treatment targets for patients with brain metastasis.
Citation Format: Stephanie Mok, Lee-Cyn Ang, Christopher J. Howlett, Zia A. Khan. Neovascularization in brain metastasis is through both angiogenesis and vasculogenesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5208. doi:10.1158/1538-7445.AM2015-5208
Abstract 521: Connexin 43 and E-cadherin modulate prostate cancer cell migration
Authors: Aloliqi Abdulaziz , Zhang Ao , Brett-Morris Adina , Lathia Justin , Fraizer Gail C. 
Published: August 2015

Abstract
Connexins play a major role in cell-cell communication and form a bidirectional signaling pathway to assemble gap junctions and, along with cadherins, alter cell behaviors, such as motility. To assess the effect of Connexin 43 (Cx43) on migration of prostate cancer cells we performed two types of migration assays using shRNA Cx43 transfected PC3 cells with suppressed Cx 43. Wound healing and transwell chamber assays were used to assess the migratory potential of stably transfected shCx43-PC3 cells. When we reduced Cx 43 we saw approximately a two-fold reduction in migration of shCx43 transfected PC3 cells compared to those transfected with scramble controls. Since suppression of Cx43 reduced migration of the highly migratory PC3 cells, we wondered whether this reflected a partial loss of mesenchymal traits (e.g., motility) and acquisition of epithelial markers, (e.g.,E-cadherin expression). Using quantitative RT-PCR, E-cadherin expression was assessed in shCx43-PC3 and scramble control cells. Suppression of Cx43 increased E-cadherin mRNA levels 5-fold or greater in shCx43-PC3 cells than in scramble control cells. An alternative approach used to transcriptionally up-regulate E-cadherin mRNA in PC3 cells (via suppression of a transcriptional repressor) resulted in a similar approximately 2.5-fold suppression of migration as measured by wound healing and transwell chamber assays. Thus, an inverse relation of Cx 43 and E-cadherin was observed in prostate cancer cells and alterations in either led to aberrant migration. These results were consistent with our hypothesis that differential connexin expression in prostate cancer cells contributes to different metastatic potential. To correlate differential connexin subunit expression with migratory potential, we quantified gene expression of 13 different Connexin subunits in non-invasive LNCaP and in invasive PC3 cells using qRTPCR. In LNCaP cells we observed low levels of Cx43 along with high levels of Cx32 and E-cadherin expression and the converse in PC3 cells. Overall, these results suggest that reducing high levels of Cx43, associated with enhanced E-cadherin expression and reduced migratory behavior could potentially block lethal metastatic tumor progression of prostate cancer cells.
Citation Format: Abdulaziz Aloliqi, Ao Zhang, Adina Brett-Morris, Justin Lathia, Gail C. Fraizer. Connexin 43 and E-cadherin modulate prostate cancer cell migration. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 521. doi:10.1158/1538-7445.AM2015-521
Abstract 522: Involvement of Zyxin in aggressiveness of human prostate cancer
Authors: Yamamoto Kei , Hori Yasuki , Seo Jieun , Hashimoto Saho , Endo Yoshihiro , Nittami Tadashi , Ito Yusuke , Ishiguro Hitoshi , Uemura Hiroji , Watanabe Masatoshi 
Published: August 2015

Abstract
Many epidemiological studies have shown that abdominal obesity was associated with an increased risk in several malignancies. The association between prostate cancer risk and obesity has been also investigated, but has been in dispute. The involvement of adipocytokines as putative molecular mediators between prostate cancer and obesity has been also investigated. We have already shown effects of conditioned medium (CM) from adipocyte culture in behaviors of prostate cancer cells (DU145). In this study, Phospho-peptide in DU145 cells cultured in CM was analyzed using Liquid chromatography-tandem mass spectrometry (LC-MS/MS). Zyxin was identified as a CM-related phosphor-peptide. Zyxin is a conserved protein that has two major domains, an N-terminal half containing proline-rich sequences and a C-terminal LIM domain region. Its functions are involved in regulation of cell adhesion and motility. This protein also appears to have tumor suppressor activity with a few reports, however in dispute. We analyzed the involvement of Zyxin in behavior of DU145 cells. Functional analysis of Zyxin in cell migration, invasive potential and others of DU145 cells was conducted using Zyxin siRNA. Knockdown of Zyxin by siRNA in DU145 cells inhibited cell migration and invasion. As for clinical paired samples, Zyxin expression in tumor tissues was higher than in normal tissues by real-time PCR. These results suggest that Zyxin may play an important role in aggressiveness of human prostate cancer.
Citation Format: Kei Yamamoto, Yasuki Hori, Jieun Seo, Saho Hashimoto, Yoshihiro Endo, Tadashi Nittami, Yusuke Ito, Hitoshi Ishiguro, Hiroji Uemura, Masatoshi Watanabe. Involvement of Zyxin in aggressiveness of human prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 522. doi:10.1158/1538-7445.AM2015-522
Abstract 5225: Endothelial-specific Jagged1 blockade prevents solid tumor growth in pre-clinical models
Authors: Duarte Antonio , Pedrosa Ana-Rita , Trindade Alexandre , Carvalho Catarina , Graça José , Carvalho Sandra , Peleteiro Maria C. , Adams Ralf H. 
Published: August 2015

Abstract
Angiogenesis is an essential process required for tumor growth and progression. The Notch signaling pathway has been identified as a key regulator of the neo-angiogenic process. Jagged-1 (Jag1) is a Notch ligand required for embryonic and retinal vascular development. Although its role as a pro-angiogenic ligand has been thoroughly studied in developmental contexts, the real contribution of this Notch ligand to tumor angiogenesis remains unknown.
The current study addresses the role of endothelial Jagged1-mediated Notch signaling in the context of tumoral angiogenesis in two different mouse tumor models: subcutaneous Lewis Lung Carcinoma (LLC) tumor transplants and the autochthonous Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP).
The role of endothelial Jagged1 in tumor growth and neo-angiogenesis was investigated with endothelial-specific Jag1 gain- and loss-of-function mouse mutants (eJag1OE and eJag1cKO). We show that the tumor vasculature of eJag1OE mutants presents increased vessel density, branching, and perivascular maturation, causing increased tumor perfusion. Ultimately, this leads to increased proliferation and survival of tumor cells, and increased epithelial-to-mesenchymal transition (EMT) resulting in increased LLC tumor growth as well as development and progression of prostate adenocarcinoma in mice. In contrast, in eJag1cKO mutants the vasculature is characterized by decreased vessel density, branching, and perivascular maturation, which restricts tumor vascular perfusion and increases vascular extravasation. This vascular phenotype leads to decreased proliferation and increased death of tumor cells, reduced EMT culminating in decreased LLC growth as well as inhibited development and progression of prostate adenocarcinoma in mice. Therefore, endothelial Jagged1 may constitute a novel promising target for solid cancer therapy.
Note: This abstract was not presented at the meeting.
Citation Format: Antonio Duarte, Ana-Rita Pedrosa, Alexandre Trindade, Catarina Carvalho, José Graça, Sandra Carvalho, Maria C. Peleteiro, Ralf H. Adams. Endothelial-specific Jagged1 blockade prevents solid tumor growth in pre-clinical models. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5225. doi:10.1158/1538-7445.AM2015-5225
Abstract 5226: Glioma stem cells internalize perivascular bevacizumab via a non-canonical pathway and target it for recycling or degradation
Authors: Muller-Greven Gaelle , Carlin Cathleen , Lathia Justin , Prayson Richard , Ahluwalia Manmeet , Toms Steven , Bredel Markus , Rich Jeremy , Hamerlik Petra , Gladson Candece L. 
Published: August 2015

Abstract
Antiangiogenic therapy shows great promise for treatment of cancer. Bevacizumab is a humanized mAb that blocks VEGF-A, thereby inhibiting angiogenesis. It has received FDA approval for patients with recurrent glioblastoma (GBM); however, approximately 30% of patients are non-responsive and the underlying mechanism for the lack of response is not known. It has been assumed that Bevacizumab solely targets circulating VEGF-A; however, VEGF-A found in the perivascular space of GBM tumors could also be an important target. We hypothesized that Bevacizumab is transcytosed across brain endothelial cells (ECs), gains access to the perivascular niche containing glioma stem cells (GSCs), and that differences in GSC endocytosis and trafficking of Bevacizumab to either a recycling or degradation compartment determines a patients’ response. We found that Bevacizumab is internalized by normal and tumor-isolated brain ECs in a time-dependent manner. ECs transcytose 20% of Bevacizumab after 30 minutes, and 40% after 120 minutes. Importantly, we found that 95% of GSCs internalize Bevacizumab within 30 minutes. Internalized Bevacizumab in GSCs can be recycled to the extracellular space via a Rab4+ fast recycling compartment, or degraded via trafficking to the LAMP1+ compartment (late endosome/lysosome). Furthermore, Bevacizumab internalization in GSCs was partially inhibited by a macropinocytosis inhibitor (EIPA) suggesting macropinocytosis is one mechanism of internalization. GSCs do not internalize Bevacizumab via the canonical IgG internalization pathway since they do not express the neonatal Fc Receptor (FcRn). Supporting our in vitro data, we found a gradient of Bevacizumab extending from the vessel into the tumor in an orthotopic xenograft mouse model of GBM administered Bevacizumab, and Bevacizumab was readily detected within perivascular tumor cells. Our data suggest that the transcytosis of Bevacizumab by brain and tumor-associated ECs, and the endocytosis and trafficking of Bevacizumab by perivascular GSCs influences Bevacizumab effectiveness in patients with GBM.
Citation Format: Gaelle Muller-Greven, Cathleen Carlin, Justin Lathia, Richard Prayson, Manmeet Ahluwalia, Steven Toms, Markus Bredel, Jeremy Rich, Petra Hamerlik, Candece L. Gladson. Glioma stem cells internalize perivascular bevacizumab via a non-canonical pathway and target it for recycling or degradation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5226. doi:10.1158/1538-7445.AM2015-5226
Abstract 527: Ectopic expression of truncated IFIT2 at C-terminal tetratricopeptide repeats enhances the migration activity of oral squamous cell carcinoma cells
Authors: Regmi Prabha , Lee Te-Chang 
Published: August 2015

Abstract
Interferon-induced protein with tetratricopeptide repeats 2 (IFIT2) belongs to one of interferon-stimulated gene family that comprise of tetratricopeptide repeats (TPR). TPR repeats are thought to mediate protein-protein interaction. Our previous report suggests that depletion of IFIT2 enhances cell migration and metastatic activity in oral squamous cell carcinoma (OSCC) cells via activation of atypical PKC signaling. However, the exact mechanism by which IFIT2 depletion activates the aPKC signaling pathway also remains unknown. Since IFIT2 comprises of nine TPR repeats, this study aims to explore the role of TPR in functioning of IFIT2. To address the above questions, different stable cell lines of truncated forms of IFIT2 were subjected to cell migration assay. Interestingly, C-terminal depleted cells exhibited increased migration ability and also showed loss of cell polarity thus leading to random cell orientation. Furthermore, these depleted cells also showed altered expression of junction proteins such as Claudin-1 and E-cadherin in comparison to IFIT2 overexpressed cells. Taken together, C-terminal depleted cells exhibit features of loss of function of IFIT2 suggesting the possible role of terminal TPR domain in maintaining the functional role of IFIT2. To identify specific TPR domain, different mutation construct are generated and its functional role is under study.
Citation Format: Prabha Regmi, Te-Chang Lee. Ectopic expression of truncated IFIT2 at C-terminal tetratricopeptide repeats enhances the migration activity of oral squamous cell carcinoma cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 527. doi:10.1158/1538-7445.AM2015-527