bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4984: Contribution of MMP13 to tumor development in the steatotic liver microenvironment
Authors: Mendonsa Alisha Maria , VanSaun Michael N. , Gorden Lee 
Published: May 2015

Abstract
With the rising prevalence of obesity there has been a marked increase in the incidence of non alcoholic fatty liver disease (NAFLD). Epidemiologically, NAFLD has been linked to an increased risk for development of primary liver cancer (HCC), however the mechanisms involved are not known. The liver is also a frequent site of metastasis for several types of cancers. To determine the effect of steatosis (fatty liver) on tumor metastasis to the liver, we used a mouse model of diet induced steatosis coupled with the splenic injection model of metastasis to the liver and found a significant increase in the number of tumors in the steatotic livers. To evaluate what molecular changes distinguish the steatotic liver from normal liver, microarray analysis was performed and demonstrated that MMP13, a member of the Matrix Metalloproteinase family recognized to be involved in liver disease and cancer progression, is significantly upregulated in the steatotic liver compared to normal livers of mice. We evaluated MMP13 expression in human patients with NAFLD and found that MMP13 is elevated with the progression of NAFLD. We hypothesize that increased MMP13 levels in the steatotic liver contribute to a more permissive microenvironment for the establishment of liver tumors. To test this hypothesis, mice genetically deficient in MMP13 or control wildtype mice, with and without steatosis, were injected with syngeneic MC38 colon cancer cells. Examination of the two groups demonstrated a significant decrease in the number of tumors in the MMP13 null mice (P &lt;0.01). Additionally, since the tumor cells themselves express MMP13, wildtype mice were injected with either shRNA control or MMP13 knockdown MC38 colon cancer cells to determine the role of tumor cell derived MMP13. Using transwell migration assay and the platypus invasion system with parental and MMP13 shRNA knockdown MC38 cells we found that loss of MMP13 decreases the invasive and migratory properties of the metastatic cancer cells in vitro. In conclusion, we found that MMP13 is elevated in the setting of steatosis and that loss of both stromal and tumor derived MMP13 lead to decreased number of metastatic foci in the liver. Tumor derived MMP13 effects tumor cell migration and invasion invitro. MMP13 may thus be a potential target to control initiation and growth of metastatic cancer of the liver.
Citation Format: Alisha Maria Mendonsa, Michael N. VanSaun, Lee Gorden. Contribution of MMP13 to tumor development in the steatotic liver microenvironment. [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 4984. doi:10.1158/1538-7445.AM2014-4984
Abstract 4989: Desmocollin 2 suppresses lung cancer cell migration and invasion through down-regulation of NDRG1 expression
Authors: Hsu Yu-Chih , Ou Po-Chun , Chen Yu-Yi , Tsai Meng-Feng 
Published: May 2015

Abstract
Desmocollin-2 (Dsc2), a calcium-dependent transmembrane glycoprotein, is the most widely distributed form of desmocollins that plays a critical role in the maintenance of normal tissue architecture in epithelia. Reduced expression of Dsc2 has been reported in colorectal carcinomas, suggesting that Dsc2 may play a role in the development and progression of colorectal cancer. Recently, down-regulated of Dsc2 expression was also found in breast, esophageal, and lung carcinomas. Dsc2 may act as tumor suppressor in various cancers. However, the role of the Dsc2 in lung cancer cells is still unclear. In this study, we report that knockdown Dsc2 expression using small-hairpin RNA (shRNA) approach can promote lung cancer cell migration and invasion abilities. Consistent with these findings, ectopic expression of Dsc2 inhibited cell migration and invasion in lung cancer cells. Additionally, we also suggested that Dsc2 inhibited lung cancer cells motility and epithelial to mesenchymal transition (EMT) through down-regulate NDRG1 and Slug expression.
Citation Format: Yu-Chih Hsu, Po-Chun Ou, Yu-Yi Chen, Meng-Feng Tsai. Desmocollin 2 suppresses lung cancer cell migration and invasion through down-regulation of NDRG1 expression. [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 4989. doi:10.1158/1538-7445.AM2014-4989
Abstract 4990: Epidermal growth factor-induced expression of PTX3 regulates metastasis of head and neck squamous cell carcinoma
Authors: Chen Ben-Kuen , Wu Shuo-Lun , Tsai Jhih-Peng 
Published: May 2015

Abstract
Overexpression of epidermal growth factor receptor (EGFR) and production of proinflammatroy cytokines are common in head and neck squamous cell carcinoma (HNSCC) and correlates with enhanced invasion and metastasis. However, molecular mechanisms associated with activation of EGFR and productions of cytokines in regulating metastasis of HNSCC remain poorly understood. Here, we identified PTX3 as a metastasis-promoting factor in HNSCC to regulate EGF-induced metastasis. We found that EGF induced the expression of PTX3, and was mediated through transcriptional activation, but not through mRNA stability. The involvement of Akt/NF-κB and AP-1 signaling pathways in the EGF-induced PTX3 gene expression was confirmed by knockdown of RelA and c-Jun, respectively. The expression of dominant negative IκB also repressed the activation of NF-κB and inhibited EGF-induced PTX3 expression. Furthermore, EGF increased the binding of NF-κB and c-Jun to the AP-1 binding site of the PTX3 promoter through the activation of the Akt/NF-κB pathway, which resulted in activating PTX3 promoter activity. In addition, EGF stimulated the secretion of PTX3 from cancer cells, resulting in enhancing cancer metastasis and the interaction between cancer cells and endothelial cells. EGF-enhanced metastasis-related molecules, such as fibronectin and MMP-9, and reduction of E-cadherin were reversed in PTX3 knockdown cells. These findings suggest that autocrine production of EGF-induced PTX3 regulates metastasis of HNSCC by mediating the expression levels of metastatic molecules fibronectin, MMP-9 and E-cadherin. The EGF-induced PTX3 could be a potential diagnostic marker and target for metastasis in the cancer therapy.
Citation Format: Ben-Kuen Chen, Shuo-Lun Wu, Jhih-Peng Tsai. Epidermal growth factor-induced expression of PTX3 regulates metastasis of head and neck squamous cell carcinoma. [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 4990. doi:10.1158/1538-7445.AM2014-4990
Abstract 4993: IFI27 and NOV, downstream regulated genes by S100A4, are playing important roles in pancreatic carcinogenesis
Authors: Chen Na , Saiki Yuriko , Sekine Hitoshi , Sunamura Makoto , Fukushige Shinichi , Motoi Fuyuhiko , Egawa Shinichi , Unno Michiaki , Horii Akira 
Published: May 2015

Abstract
S100A4 is a member of the Ca2+-dependent S100 protein family, and positive association between S100A4-upregulation andmetastasis/invasion was reported. We reported a significant association between upregulation of S100A4 and perineural invasion in pancreatic cancer. Furthermore, siRNA-mediated knockdown of S100A4 promoted cell death mainly mediated by induction of apoptosis only in cancer cells with high expression of S100A4, and forced expression of S100A4 induced accelerated cell motility only in cancer cells with low expression. To explore the molecular mechanisms of cell motility after the forced expression of S100A4, we analyzed gene expression profiles and identified some candidate genes including IFI27 and NOV (CCN3) that are regulated by S100A4-upregulation, and we further focused on IFI27 and NOV. IFI27 showed significant upregulation after the forced expression of S100A4 and downregulation after siRNA mediated knockdown of S100A4, while NOV seemed to show an inverse relationship with S100A4. Using 93 primary resected tumors, we performed immunohistochemical analyses and identified significant positive association between S100A4 and IFI27 expressions. Although NOV did not show significant inverse-association, siRNA-mediated knockdown in high level expressing cells showed significant acceleration of cell motility. Clinicopathologic characteristics demonstrated positive associations between IFI27 expression and intrapancreatic neural invasion (P=0.0023) and negative associations between NOV expression and invasion pattern (P=0.017) were observed. Our present study suggests that IFI27 and NOV may be downstream regulated genes of S100A4 and that expressional changes may play important roles in invasion of pancreatic cancer.
Citation Format: Na Chen, Yuriko Saiki, Hitoshi Sekine, Makoto Sunamura, Shinichi Fukushige, Fuyuhiko Motoi, Shinichi Egawa, Michiaki Unno, Akira Horii. IFI27 and NOV, downstream regulated genes by S100A4, are playing important roles in pancreatic carcinogenesis. [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 4993. doi:10.1158/1538-7445.AM2014-4993
Abstract 4996: Interferon consensus sequence binding protein (ICSBP) promotes epithelial to mesenchymal transition (EMT)-like phenomena, cell motility, and invasion via TGF-β signaling in U2OS cells
Authors: Sung Jee Young , Park Seog-Yun , Kim June Hyuk , Kang Hyun Guy , Yoon Jong Hyung , Na Yoon Sook , Kim Yong-Nyun , Park Byung-Kiu 
Published: May 2015

Abstract
Interferon consensus sequence binding protein (ICSBP) is a transcription factor induced by interferon gamma (IFN-γ) and a member of the interferon regulatory factor (IRF) family. ICSBP is predominantly expressed in hematopoietic cells and regulates the immune response and cell growth and differentiation. However, little is known about its function in non-hematopoietic cells. Here we show a novel function for ICSBP in epithelial to mesenchymal transition (EMT)-like phenomena (ELP), cell motility, and invasion in human osteosarcoma cell lines, including U2OS cells. IFN-γ treatment induced ICSBP expression and EMT-like morphological change in U2OS cells, which were suppressed by ICSBP knock-down. To further investigate the role of ICSBP in ELP, we established a stable U2OS cell line that overexpresses ICSBP. ICSBP expression caused U2OS cells to have a more elongated shape and an increased vimentin and fibronectin expression. ICSBP expression also promoted adhesiveness, motility, and invasiveness of U2OS cells. ICSBP up-regulated transforming growth factor (TGF)-β receptors and activated TGF-β signaling cascades, which were responsible for ELP as well as increased cell motility and invasion. In addition, ICSBP-induced TGF-β receptor activation resulted in the up-regulation of Snail. Knock-down of Snail attenuated the ICSBP-induced augmentation of cell motility and invasion. Up-regulation of Snail, ELP, and increased invasion by ICSBP expression were also observed in other osteosarcoma cell lines, such as Saos-2 and 143B. Furthermore, ICSBP and TGF- β receptor I were expressed in 45/54 (84%) and 47/54 (87%) of human osteosarcoma tissues, respectively, and showed significant correlation (r= 0.47, p= 0.0007) with respect to their expression levels. Taken altogether, these data demonstrate a novel function for ICSBP in ELP, cell motility, and invasion through the TGF-β and Snail signaling pathways
Citation Format: Jee Young Sung, Seog-Yun Park, June Hyuk Kim, Hyun Guy Kang, Jong Hyung Yoon, Yoon Sook Na, Yong-Nyun Kim, Byung-Kiu Park. Interferon consensus sequence binding protein (ICSBP) promotes epithelial to mesenchymal transition (EMT)-like phenomena, cell motility, and invasion via TGF-β signaling in U2OS 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 4996. doi:10.1158/1538-7445.AM2014-4996
Abstract 4997: MMP14 as PTP4A3 downstream target is involved in uveal melanoma cell dissemination
Authors: Maacha Selma 
Published: May 2015

Abstract
Abstract: Uveal melanoma is the most common intraocular malignancy in adults, representing 5% of all melanomas. Although at diagnosis over 95% of patients have disease limited to the eye, about 50% will develop metastases after a median period of 36 months. High expression levels of Protein Tyrosine Phosphatase 4A3 (PTP4A3), a dual phosphatase, is highly predictive of metastasis development and PTP4A3 overexpression in uveal melanoma cells increases their in vitro migration and in vivo invasiveness. The PTP4A3 mechanism of action in the tumoral process is poorly understood. We identified the metalloprotease MMP14 as an interacting partner of PTP4A3. MMP14 is more abundant at the cell membrane in PTP4A3 invasive cells compared to control cells (inactive catalytic site mutant GFP-PTP4A3(C104S) or EGFP) and inhibition of MMP14 expression decreases PTP4A3-induced cell invasiveness. The MMP14-differential cell membrane localization in presence of PTP4A3 is currently investigated by studying the trafficking of MMP14 in these cells.
Citation Format: Selma Maacha. MMP14 as PTP4A3 downstream target is involved in uveal melanoma cell dissemination. [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 4997. doi:10.1158/1538-7445.AM2014-4997
Abstract 4999: Paracrine regulation of glioma invasion by astrocytes is mediated by glial derived neurothropic factor
Authors: Amit Moran , Shabtay-Orbach Ayelet , Binenbaum Yoav , Gil Ziv 
Published: May 2015

Abstract
Purpose: Glial cells have been shown to play a role in glioma progression. Here we investigate the mechanism by which astrocytes which are abundant in glioma tumors, promote cancer cell invasion.
Experimental Design: In this study, we evaluated the effects of astrocytes on glioma biology both in vitro and in vivo and determined the downstream paracrine effect of glial derived neurotropic factor (GDNF) on tumor invasion.
Results: Astrocytes conditioned media (ACM) significantly increased human and murine glioma cells migration compared to controls. This effect was inhibited when the activity of GDNF on glioma cells was blocked by RET-Fc chimera or anti-GDNF Ab and by siRNA directed against GDNF expression by astrocytes. Glioma cell incubation with ACM led to time dependent phosphorylation of the GDNF receptor, RET and downstream AKT phosphorylation. Tumor migration and GDNF-RET-AKT activation was inhibited by the RET small molecule inhibitor pyrazolopyrimidine-1 and by the AKT inhibitor LY294002. Finally, blocking of RET by pyrazolopyrimidine-1 or knockout of the RET co receptor GFRα1 in glioma cells reduced the size of brain tumors in immunocompetent mice.
Conclusions: We suggest a mechanism by which astrocytes attracted to the glioma microenvironment facilitate brain invasion by secretion of GDNF and activation of RET/GFRα1 receptors expressed by the cancer cells.
Note: This abstract was not presented at the meeting.
Citation Format: Moran Amit, Ayelet Shabtay-Orbach, Yoav Binenbaum, Ziv Gil. Paracrine regulation of glioma invasion by astrocytes is mediated by glial derived neurothropic factor. [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 4999. doi:10.1158/1538-7445.AM2014-4999
Abstract 5: Real-time in vivo imaging of osteosarcoma angiogenesis
Authors: Uehara Fuminari , Tome Yasunori , Maehara Hiroki , Kanaya Fuminori , Miwa Shinji , Hiroshima Yukihiko , Yano Shuya , Yamamoto Mako , Matsumoto Yasunori , Hoffman Robert M. 
Published: May 2015

Abstract
We report here real-time color-coded imaging of osteosarcoma-induced angiogenesis in vivo. Gelfoam® (5×5 mm) treated with β fibroblast growth factor (bFGF) was initially transplanted subcutaneously in the flank of transgenic nestin-driven green fluorescent protein (ND-GFP) nude mice (n=12). In ND-GFP mice, nascent blood vessels are labeled with GFP, including those growing in Gelfoam®. Seven days after transplantation of Gelfoam®, skin flaps were made and human 143B osteosarcoma cells expressing GFP in the nucleus and red fluorescent protein (RFP) in the cytoplasm were injected into the transplanted Gelfoam®. The control group had only Gelfoam® transplanted without subsequent cancer-cell inoculation. Skin flaps were made at days 14, 21, 28 after transplantation of the Gelfoam® to allow observation of vascularization of the Gelfoam® using fluorescence imaging after both with and without cell inoculation. ND-GFP expressing nascent blood vessels penetrated and spread into the Gelfoam® in both the non-cellular control and after cancer-cell inoculation. The mean length of ND-GFP expressing blood vessels of mice with osteosarcoma cells seeded on the Gelfoam® increased compared to the Gelfoam®-only control at days 14, 21, 28 after transplantation of the Gelfoam® (at day 14, 21 ; p&lt;0.05, at day 28 ; p&lt;0.01). The results demonstrate that the osteosarcoma cells stimulated angiogenesis within the Gelfoam®. This model enables facile imaging of cancer-cell-induced angiogenesis and the study of its mechanism and inhibition.
Citation Format: Fuminari Uehara, Yasunori Tome, Hiroki Maehara, Fuminori Kanaya, Shinji Miwa, Yukihiko Hiroshima, Shuya Yano, Mako Yamamoto, Yasunori Matsumoto, Robert M. Hoffman. Real-time in vivo imaging of osteosarcoma angiogenesis. [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 5. doi:10.1158/1538-7445.AM2014-5
Abstract 5008: The acetylenic tricyclic bis(cyanoeneone), TBE-31 inhibits non-small cell lung cancer cell migration through direct binding with actin
Authors: Chan Eddie , Saito Akira , Honda Tadashi , Guglielmo John D. 
Published: May 2015

Abstract
During metastasis tumor cells undergo epithelial to mesenchymal transition (EMT), where cell-cell junctions dissolve and actin stress fibers are formed. This transition unmasks the migratory and invasive potential of the tumor cells. Here we show that the tricyclic compound TBE-31 binds to purified actin as well as actin from cell lysates. Furthermore, TBE-31 inhibits linear and branched actin polymerization in vitro as well as stress fiber formation in fibroblasts. We also observed that TBE-31 inhibits stress fiber formation in non-small lung cancer cells during TGFβ-dependent EMT. Interestingly, TBE-31 does not interfere with TGFβ-dependent signaling or changes in E- and N-cadherin protein levels during EMT. Finally, we observed that TBE-31 inhibits non-small cell lung tumor cell migration. Our results suggest that TBE-31 targets linear actin polymerization to alter cell morphology and inhibit cell migration.
Citation Format: Eddie Chan, Akira Saito, Tadashi Honda, John Di Guglielmo. The acetylenic tricyclic bis(cyanoeneone), TBE-31 inhibits non-small cell lung cancer cell migration through direct binding with actin. [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 5008. doi:10.1158/1538-7445.AM2014-5008
Abstract 5009: Thymoquinone downregulates n-cadherin, twist and snail expression and inhibits migration and invasion in cancer cells
Authors: Khan Md. Asaduzzaman , Yang Manman , Wei Chunli , Gan Lin , Fu Junjiang 
Published: May 2015

Abstract
Background: Metastasis is the major characteristic of malignant carcinomas, which has been found to be linked with epithelial to mesenchymal transitions (EMT). Regulation of EMT process can provide a significant beneficiary effect to control metastasis, as well as to treat cancers. In this study we have investigated the effects of natural product Thymoquinone in metastatic cancer cell lines to evaluate their role in metastatic characteristics linked to EMT process.
Methods: We have treated HeLa and MDA-MB-435 human cancer cell lines with Thymoquinone, and analyzed the cell proliferation, migration and invasion, which are the major metastatic characteristics, by using the real-time cell analyzer. The real-time PCR and Western blot analysis was employed for the determination of the cellular expression of major EMT-associated proteins N-cadherin and E-cadherin; their transcription factors Twist, Snail, Slug and Zeb; and another important metastatic protein Vimentin.
Results: Thymoquinone was found to inhibit the migratory and invasive characteristics in both cancer cell lines dose dependently, and effective in a low dose eventually (1-5 μM). Its cytotoxicity has also been confirmed by MTT assay for cell viability. Genetic expression analysis showed that Thymoquinone significantly down-regulates the mRNA expression of cell adhesion protein N-cadherin in HeLa cell. Thymoquinone also down-regulates the transcription factor Twist, which is being considered as an oncoprotein. Thymoquinone has mild to moderate effect on the expression pattern of other metastatic proteins in HeLa cells. In MDA-MB-435, Thymoquinone treatment downregulates Twist, Snail, Vimentin and N-cadherin. However, N-cadherin expression was found in extremely low in both untreated and treated MDA-MB-435.
Conclusions: We report that the prospective anticancer molecule Thymoquinone down-regulates N-cadherin and its transcription factors like Twist and Snail, which might have a significant influence on the effects of Thymoquinone in controlling cell migration and invasion. Further research is necessary for the investigation of this compound in specific cancer types with mechanisms in detail.
Fund support: This work was supported in part by the National Natural Science Foundation of China (81172049, 30371493), Science and Technology Innovation Team of Colleges and Universities of Sichuan Province (13TD0032).
Citation Format: Md. Asaduzzaman Khan, Manman Yang, Chunli Wei, Lin Gan, Junjiang Fu. Thymoquinone downregulates n-cadherin, twist and snail expression and inhibits migration and invasion in cancer 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 5009. doi:10.1158/1538-7445.AM2014-5009