bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2612: Tumor associated microvesicles confer neoplastic transformation of patient derived adipose stem cells .
Authors: Abd Elmageed Zakaria Y. , Yang Yijun , Thomas Raju , Moparty Krishnarao , Ranjan Manish , Mondal Debasis , Moroz Krzysztof , Sartor Oliver , Abdel-Mageed Asim B. 
Published: August 2014

Abstract
Background: Unraveling the underlying mechanisms of prostate tumor growth and metastasis is critical to developing curative therapies currently unavailable for castration-resistant prostate cancer (CRPC). Obesity has been linked to increased risks of PC progression. Emerging evidence suggests that adipose-derived stem cells (ASCs) are often recruited to and promote tumor growth via unknown mechanisms.
Methods: Patient derived ASCs (pASCs) with tumor homing potential were enriched and treated with condition media (CM) or microvesicles (MVs) of PC (C4-2B, PC-3) or normal prostate epithelial (RWPE1) cells. CM or MV-primed pASCs were examined for their ability to form prostate tumors in vivo. Tumor formation was validated by histopathologic analysis, expression of neoplastic and vasculogenic markers, karyotyping and PC specific markers. LC/MS-MS, miRNA array, miRNA mimics and qRT-PCR analyses were employed to decipher the underling mechanistic roles of oncogenic RNAs and proteins of PC cell associated MVs in pASC tumor formation.
Results: Herein, we report that PC cell microenvironment induces genotypic and phenotypic changes in pASCs and subverts them to undergo neoplastic transformation. Unlike normal counterparts, the pASCs primed with PC cell CM form neoplastic lesions in vivo and reproduce aggressive tumors in secondary recipients. The pASC tumors acquire cytogenetic aberrations and express epithelial, neoplastic and vasculogenic markers reminiscent of molecular features of PC tumor xenografts and mesenchymal-to-epithelial transition (MET). MVs derived from PC cell CM recapitulated prostate tumorigenic mimicry by pASCs in vivo. The oncogenic ‘reprogramming’ of pASCs is associated with PC cell-derived MVs transfer of oncomiRNAs (miR-125b, miR-130b, miR-155), H-Ras and K-Ras transcripts and Ras-related oncoproteins (RAB1A, RAB2A, RAB1B, RAB11A) and down-regulation of tumor suppressors Lats2 and PDCD4.
Conclusion: Our findings establish previously uncharacterized mechanisms for tumor-derived MV-pASC axis in tumor formation, phenotypic variations in mesenchymal and epithelial states in tumor microenvironment, and in promoting tumor burden and metastasis in cancer patients.
Citation Format: Zakaria Y. Abd Elmageed, Yijun Yang, Raju Thomas, Krishnarao Moparty, Manish Ranjan, Debasis Mondal, Krzysztof Moroz, Oliver Sartor, Asim B. Abdel-Mageed. Tumor associated microvesicles confer neoplastic transformation of patient derived adipose stem cells . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2612. doi:10.1158/1538-7445.AM2013-2612
Abstract 2613: Prostate cancer stem/initiating cells are targets of both innate and adaptive immunity and elicit potent immune responses against autochthonous prostate tumors.
Authors: Jachetti Elena , Mazzoleni Stefania , Grioni Matteo , Ricupito Alessia , Brambillasca Chiara , Generoso Luca , Calcinotto Arianna , Freschi Massimo , Mondino Anna , Galli Rossella , Bellone Matteo 
Published: August 2014

Abstract
Purpose. Objectives of this study were to investigate if prostate cancer stem/initiating cells (CSC) obtained from autochthonous tumors possess the molecular characteristics that allow their in vitro and in vivo recognition by cells of the innate and/or adaptive arms of the immune system, and if CSC are source of antigens for the induction of tumor-specific immune responses.
Material and Methods. CSC lines established from the prostate of transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were assessed in vitro for the expression of tumor-associated antigens and susceptibility to NK and T cell killing. We also investigated NK and T cells immune surveillance against CSC by measuring the frequency of CSC-induced tumors in immunocompetent and selectively immunodeficient mice. Finally, we assessed if vaccination with dendritic cells pulsed with CSC induced a tumor-specific immune response able to delay the growth of both transplantable and autochthonous prostate tumors.
Results. CSC expressed prostate cancer associated antigens, MHC I and MHC II molecules and ligands for natural killer (NK) cells. Indeed, CSC were targets of NK and cytotoxic T lymphocytes both in vitro and in vivo. Vaccination with dendritic cells pulsed with apoptotic CSC induced a tumor-specific immune response that delayed tumor growth in mice challenged with prostate CSC, and caused tumor regression in TRAMP mice.
Conclusions. CSC are targets of both innate and adaptive immune responses and could be exploited for the design of novel immunotherapeutic approaches against cancer.
Citation Format: Elena Jachetti, Stefania Mazzoleni, Matteo Grioni, Alessia Ricupito, Chiara Brambillasca, Luca Generoso, Arianna Calcinotto, Massimo Freschi, Anna Mondino, Rossella Galli, Matteo Bellone. Prostate cancer stem/initiating cells are targets of both innate and adaptive immunity and elicit potent immune responses against autochthonous prostate tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2613. doi:10.1158/1538-7445.AM2013-2613
Abstract 262: The evolution of diverse cancer stem cells in human liver cancer.
Authors: Yamashita Taro , Honda Masao , Nio Kouki , Hara Yasumasa , Hayashi Takehiro , Oishi Naoki , Sunakozaka Hajime , Takatori Hajime , Kaneko Shuichi 
Published: August 2014

Abstract
Cancer stem cells (CSCs) are considered a pivotal target for the eradication of liver cancer. CSCs have been identified by the use of various stem cell markers; however, it remains unclear how individual CSC markers are expressed in individual tumors. We hypothesized that the distinct marker-positive CSCs show unique features of tumorigenicity/metastasis and chemosensitivity which may reflect the heterogeneous nature of hepatocellular carcinoma (HCC). Gene expression profiling and immunohistochemistry analyses were used to analyze 364 tumor specimens. Fluorescence-activated cell sorting (FACS) was used to isolate marker-positive HCC cells, which were tested for hepatic stem/progenitor cell properties. CSC markers EpCAM and CD90 are independently expressed in primary liver cancer. EpCAM+ cells share features with tumorigenic epithelial stem cells, whereas CD90+ cells share those of metastatic vascular endothelial cells with expression of c-Kit. CD90+ cells facilitate metastasis of EpCAM+ cells through activation of TGF-beta signaling, and this effect is abolished by c-Kit inhibitor imatinib mesylate. These distinct tumorigenic/metastatic CSCs can evolve from marker-negative cells de novo, and their frequencies vary dramatically according to the genomic alterations and genotoxic stress. Our results suggest that liver CSCs are not a single, static entity but rather exist heterogeneously and undergo dynamic changes through genomic alteration and genotoxic stress. The evolution of CSCs explains the enrichment of CSCs in advanced cancer and the limitation of targeting marker-positive CSCs alone for tumor eradication.
Citation Format: Taro Yamashita, Masao Honda, Kouki Nio, Yasumasa Hara, Takehiro Hayashi, Naoki Oishi, Hajime Sunakozaka, Hajime Takatori, Shuichi Kaneko. The evolution of diverse cancer stem cells in human liver cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 262. doi:10.1158/1538-7445.AM2013-262
Abstract 2620: Progressive expression of n-cadherin and epidermal growth factor receptor in colorectal adenocarcinoma.
Authors: Katkoori Venkat R. , Manne Upender , Basson Marc D. , Bumpers Harvey L. 
Published: August 2014

Abstract
Purpose: N-cadherin (NCAD) and epidermal growth factor receptor (EGFR) have been found to be inducers of epithelial-to-mesenchymal transition that are known to play a role in invasion and metastasis of cancer. Over expression of NCAD and EGFR are associated with increased tumor invasiveness. However, their progressive expression in colorectal cancer (CRC) has not been studied. Therefore, in the present study, we investigated expression status of NCAD and EGFR in paired lesions of CRC. Experimental Design: We examined the expression of NCAD and EGFR in paired lesions of human CRC (hCRC) and human mice CRC (hmCRC) xenograft by immunofluorescence (IF). Images were acquired using the Olympus FluoView FV1000 (OFVFV1000) Confocal Microscope. The average FITC fluorescence intensity (aFFI) was measured by OFVFV1000 software. Western blot analysis was performed to validate results obtained from IF method.
Results: Differential expression pattern of NCAD was observed in paired normal, primary and metastatic lesions of hCRC and hmCRC xenograft tissues. For NCAD, it was mainly localized in cytoplasm (diffused), nucleus (moderate levels), and membrane or cell junctions of CRC. For EGFR, normal colon tissue or primary CRC showing membranous EGFR-low positive staining. In contrast corresponding liver metastasis showing membranous EGFR-high positive staining. The NCAD and EGFR expressions were correlated with metastasis phenotype of hCRC. The expressions of NCAD ((aFFI; 812 vs. 261) and EGFR (aFFI 421 vs.131) were each found to be 3 times higher in liver metastasis of hCRC as compared to primary tumor. It has been observed that the expression of NCAD was substantially increased in metastatic lesion of hmCRC xenograft as compared to primary lesion of hmCRC xenograft.
Conclusion: This study revealed that upregulation of NCAD and EGFR expressions is a mechanism by which CRC lesions acquire a more aggressive phenotype and, thereby, progress to a more advanced stage of CRC. Furthermore, our findings are likely to have implications in the design of clinical trials targeting the NCAD and EGFR proteins in CRC.
Citation Format: Venkat R. Katkoori, Upender Manne, Marc D. Basson, Harvey L. Bumpers. Progressive expression of n-cadherin and epidermal growth factor receptor in colorectal adenocarcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2620. doi:10.1158/1538-7445.AM2013-2620
Abstract 2622: TMEFF2 inhibits human prostate cancer cell migration through its G protein activating domain.
Authors: Chen Xiaofei , Justus C. , Yang L , Ruiz-Echevarria M.j. 
Published: August 2014

Abstract
The type I transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2) is expressed mainly in brain and prostate. Expression of TMEFF2 is deregulated in a significant fraction of primary and metastatic prostate, suggesting a role in this disease. In fact, we have previously shown that TMEFF2 can function as a tumor suppressor in vitro, inhibiting monolayer and anchorage-independent cellular growth in HEK293T cells and sarcosine-induced cell migration and invasion in benign prostate epithelial RWPE-1 cells. However, the molecular mechanisms involved in the tumor suppressor phenotype of TMEFF2 are not clear. TMEFF2 has several biologically important features. The extracellular domain contains two follistatin domains and an epidermal growth factor-like (EGF) domain, while the transmembrane domain and short cytoplasmic tail have features resembling a G protein activating domain, suggesting that it may signal through a G protein. We hypothesize that the tumor suppressor activity of TMEFF2 is, at least in part, due to signaling mediated by the putative G protein activating domain. In order to test this hypothesis, here we investigate the role of TMEFF2 and a mutant lacking the cytoplasmic tail on cellular migration of prostate cancer cells, and begin analyzing the molecular mechanisms involved in this effect.
Our results demonstrate that overexpression of TMEFF2 in human prostate cancer cell line RWPE-2 causes about 60% decrease in cellular migration as assessed by wound-healing assays. Interestingly, we found that RWPE-2 cells overexpressing TMEFF2 have a defect in cell spreading on culture dishes (∼20% decrease) as well as on vitronectin-coated coverslips (∼30% decrease) and that this defect is accompanied by abolished focal adhesion and stress fiber formation. Moreover, the inhibition of TMEFF2 on cellular migration is dependent on its G protein activating domain as deletion of this domain rescues migration, spreading on vitronectin, and focal adhesion formation. The specific G protein pathway(s) involved in the anti-migratory effect of TMEFF2 is currently under investigation.
In summary, the data presented here indicate, for the first time, that the anti-migratory effect of TMEFF2 in human prostate cancer cells is mediated by its G protein activating domain. These results raise the possibility that TMEFF2 agonists may be used as therapeutic agents to mediate tumor suppression via this pathway.
Citation Format: Xiaofei Chen, C. Justus, L Yang, M.j. Ruiz-Echevarria. TMEFF2 inhibits human prostate cancer cell migration through its G protein activating domain. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2622. doi:10.1158/1538-7445.AM2013-2622
Abstract 2623: Snail 1 regulates invasion through uPA-uPAR signaling using the MAPK pathway in prostate cancer cells.
Authors: Randle Diandra D. , Marah Valerie 
Published: August 2014

Abstract
Epithelial-mesenchymal transition (EMT) is a process by which cancer cells acquire mesenchymal properties, such as induction of N-cadherin, while epithelial-associated genes like E-cadherin are lost. This enables the cells to be more invasive, migratory and metastatic. Factors that can induce EMT include growth factors like transforming growth factor -β (TGF-β) and epidermal growth factor (EGF), and transcription factors like Snail1. Snail1-induced EMT promotes migration and invasion and we hypothesized that this may be mediated by urokinase (uPA) and its receptor (uPAR) activities. uPA, a serine protease, may be activated by integrin engagement to bind to its receptor, uPAR, and initiate a signaling cascade that regulates a variety of biological pathways including invasion. Androgen-dependent LNCaP and 22Rv1 and androgen-independent ARCaP human prostate cancer (PC) cells were stably transfected with empty vector control (Neo) or constitutively active Snail1 which led to increased cell migration and invasion. Superarray analysis revealed an upregulation in uPAR expression in Snail-transfected cells as compared to Neo control. Next, the protein expression levels of Snail1, uPA, and uPAR were measured by Western Blot analysis. uPA activity in conditioned media was measured using the Elisa uPA activity assay kit. Also, uPAR was transiently silenced in ARCaP Snail-overexpressing cells using uPAR siRNA. Additionally, cells were treated with MAPK inhibitor, UO126, at set time points. The data suggests that overexpression of Snail1 increased uPA and uPAR protein levels, and uPA activity was elevated in conditioned media from LNCaP, 22Rv1 and ARCaP Snail-overexpressing cells, as compared to Neo controls. Additionally, the silencing of uPAR decreased cell invasion in ARCaP Snail-overexpressing cells. Finally, MAPK inhibitor, UO126, inhibited cell invasion and decreased uPA activity. Therefore, Snail-mediated cell invasion in human prostate cancer cells may occur via the regulation of the MAPK and uPA/ uPAR signaling pathway.
Acknowledgements: These studies were supported by the: NIH/NCRR/RCMI grant G12RR03062 and NIH P20 grant 1P20MD002285.
Citation Format: Diandra D. Randle, Valerie Marah. Snail 1 regulates invasion through uPA-uPAR signaling using the MAPK pathway in prostate cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2623. doi:10.1158/1538-7445.AM2013-2623
Abstract 2625: Knockdown of death receptor 5 promotes cancer cell invasion through activation of the ERK and JNK signaling pathways.
Authors: Oh You-Take , Yue Ping , Khuri Fadlo R. , Sun Shi-Yong 
Published: August 2014

Abstract
Death receptor 5 (DR5) is a death domain-containing transmembrane receptor and can trigger apoptosis upon overexpression or ligation with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Despite of the primary function of DR5 in induction of apoptosis, accumulating evidence suggest that DR5 may also have non-apoptotic function in regulation of cancer development and progression, which is the focus of this study. Both transient and stable knockdown of DR5 did not affect the growth of cancer cells, but significantly promoted the invasive ability of cancer cells in an in vitro matrigel invasion assay. In contrast, DR5 activation by low doses of the agonistic antibody, AMG655, suppressed cancer cell invasion. Similar results could not generated by knocking down DR4 expression. Thus, DR5 negatively regulates invasion of cancer cells. Knockdown of DR5 expression was accompanied by activation of both ERK and JNK signaling pathways as evidenced by elevate levels of p-ERK, p-JNK and p-c-Jun as well as their downstream proteins c-Jun and Fra-1. Chemical (e.g., with small molecule inhibitors) or genetic (e.g., with siRNA) inhibition of either ERK or JNK blocked DR5 knockdown-induced enhancement of cell invasion. In agreement, knockdown of c-Jun and Fra-1 had similar impact on blockage of cell invasion induced by DR5 knockdown. Hence, DR5 knockdown promotes cancer cell invasion through activation of the ERK and JNK signaling pathways and subsequent activation of AP-1. Our findings highlight a novel non-apoptotic function of DR5 as a negative regulator of cancer cell invasion and provide preliminary mechanisms to account for this function.
(This study was supported by the Georgia Cancer Coalition Distinguished Cancer Scholar award, NIH/NCI SPORE P50 grant CA128613 and Winship Cancer Institute Robbins Scholar award. FR Khuri and SY Sun are Georgia Cancer Coalition Distinguished Cancer Scholars. YT Oh is a recipient of Winship Cancer Institute Robbins Scholar award)
Citation Format: You-Take Oh, Ping Yue, Fadlo R. Khuri, Shi-Yong Sun. Knockdown of death receptor 5 promotes cancer cell invasion through activation of the ERK and JNK signaling pathways. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2625. doi:10.1158/1538-7445.AM2013-2625
Abstract 2639: MicroRNA miR-99a exerts anti-tumorigiceffect through decreasing myotubularin related protein 3 expression in oralcancer.
Authors: Wu Li-Wha 
Published: August 2014

Abstract
Head and neck cancer is the six most common carcinomas worldwide. Oral cancer, one head and neck cancer subtype, is the fourth leading causes of male cancer death in Taiwan.
The deregulation of certain microRNAs has been associated with the progression and metastasis of various cancer types. MicroRNAs are noncoding RNA molecules in a length of 19∼25 nucleotides, which can mediate gene expression by base pairing to the 3’untralslated region of target mRNAs. Using human microRNA microarray analysis, we found that miR-99a was most down-regulated among 1146 miRs in oral cancer cells when compared to normal oral keratinocytes. Real-time
PCR analysis further confirmed the down-regulation of miR-99a both in both tested oral cancer cell lines and human clinical specimens. Transient and stable expression of miR-99a inhibited the migration and invasion of oral cancer cells while having differential effects on cell proliferation depending on the cell types. The introduction of anti-miR-99a, silencing the effect of miR-99a, led to the increase of cell migration and invasion. Luciferase reporter assays and site-directed mutagenesis identified MTMR3, a member of myotubularin-related genes encoding phosphatidylinositol 3-phosphate 3-phosphatases, to be a downstream target of miR-99a. Knocking down MTMR3 expression in high
MTMR3-expressing oral cancer cells significantly impaired the ability of oral cancer cells to proliferate, migrate or invade Matrigel, suggesting an oncogenic role of MTMR3 in oral cancer cells. Together, our findings suggest that miR-99a plays a repressive role in cell migration and invasion partly through regulating MTMR3 expression in oral cancer cells.
Citation Format: Li-Wha Wu. MicroRNA miR-99a exerts anti-tumorigiceffect through decreasing myotubularin related protein 3 expression in oralcancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2639. doi:10.1158/1538-7445.AM2013-2639
Abstract 2642: Multiple roles of p53-related pathways in somatic cell reprogramming and stem cell differentiation.
Authors: Yi Lan , Lu Chiwei , Hu Wenwei , Levine Arnold J. 
Published: August 2014

Abstract
The inactivation of p53 functions enhances the efficiency and decreases the latency of producing induced pluripotent stem cells (iPSC) in culture. The formation of iPSCs in culture starts with a rapid set of cell divisions followed by an epigenetic reprogramming of the DNA and chromatin. The mechanisms by which the p53 protein inhibits the formation of iPSCs are largely unknown. Employing a temperature sensitive mutant of the p53 (Trp53) gene, we examined the impact of the temporal expression of wild type p53 in preventing stem cell induction from somatic cells. We also explored how different p53 mutant alleles affect the reprogramming process. We found that little or no p53 activity favors the entire process of somatic cell reprogramming. Reactivation of p53 at any time point during the reprogramming process not only interrupted the formation of iPSCs, but also induced newly formed stem cells to differentiate. Among p53 regulated genes, p21 (Cdkn1a), but not Puma (Bbc3) played a partial role in iPSCs formation probably by slowing cell division. Activation of p53 functions in iPS cells induced senescence and differentiation in stem cell populations. High rate of birth defects and increases in DNA methylation at the IGF2-H19 loci in female offspring of p53 knockout mice suggested that the absence of p53 may give rise to epigenetic instability in a stochastic fashion. Consistently, selected p53 missense mutations showed differential effects on the stem cell reprogramming efficiency in a c-Myc dependent manner. The absence of p53 activity and functions also contributed to an enhanced efficiency of iPSC production from cancer cells. The production of iPSCs in culture from normal and cancer cells, while different from each other in several ways, both responded to the inhibition of reprogramming by the p53 protein.
Citation Format: Lan Yi, Chiwei Lu, Wenwei Hu, Arnold J. Levine. Multiple roles of p53-related pathways in somatic cell reprogramming and stem cell differentiation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2642. doi:10.1158/1538-7445.AM2013-2642