bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1405: Mesothelin enhances ovarian cancer invasion of by inducing MMP-7 through MAPK/ERK and JNK pathways
Authors: Chang Ming-Cheng , Chen Chi-An , Chiang Ying-Cheng , Chen Tzer-Ming , Cheng Wen-Fang 
Published: June 2012

Abstract
Ovarian cancer is a cancer of high mortality in women malignancies. Little is known with its property of tumor progression and no effective molecule could monitor the tumor growth or therapeutic responses of this disease. In our previous studies, we first identified that mesothelin, a secreted protein, over-expressed in ovarian cancer tissues with a poor clinical outcome in chemotherapeutic response of ovarian cancer patients. Besides, mesothelin activated PI3K/Akt signaling to inhibit paclitaxel-induced apoptosis. Here, we investigated the mechanism of mesothelin enhancing the invasion of ovarian cancer and the correlation between mesothelin and metastatic diseases. The expression of mesothelin correlated well with expression of MMP-7 in human ovarian cancer tissues. Mesothelin over-expressed or mesothelin-treated ovarian cancer cells could enhance the migration and invasion of cancer cells through the activation of MMP-7. Mesothelin could regulate the expression of MMP-7 through ERK (extracellular-signal-regulated kinase) 1/2, Akt (phosphoinositide 3-kinase), and JNK (c-jun-N-terminal kinase) pathways. The MMP-7 expression and the migrating ability of mesothelin-treated ovarian cancer cells can be suppressed by the ERK1/2 or JNK specific inhibitor, or decoy AP-1 oligonucleotide in in vitro experiments. The in vivo animal experiments also demonstrated that mice treated with MAPK/ERK or JNK- specific inhibitor could decrease the itnratumoral MMP-7 expression and delay the tumor growth. We concluded that mesothelin enhances ovarian cancer invasion by MMP-7 expression through the MAPK/ERK and JNK signal transduction pathways. And blocking these two pathways can be a potential strategy to inhibit the tumor growth of ovarian cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1405. doi:10.1158/1538-7445.AM2011-1405
Abstract 1406: Downregulation of uPAR inhibits migration, invasion, proliferation, FAK/PI3K/Akt signaling, and induces senescence in papillary thyroid carcinoma cells
Authors: Nowicki Theodore S. , Zhao Hong , Darzynkiewicz Zbigniew , Moscatello Augustine , Schantz Stimson , Shin Edward , Tiwari Raj K. , Geliebter Jan 
Published: June 2012

Abstract
Papillary thyroid carcinoma (PTC) is the most common endocrine and thyroid malignancy. The urokinase plasminogen activator receptor (uPAR) plays an important role in cancer pathogenesis, including breakdown of the extracellular matrix, invasion, and metastasis. Additionally, there is increasing evidence that uPAR also promotes tumorigenesis via the modulation of multiple signaling pathways. BRAFV600E, the most common initial genetic mutation in PTC, leads to ERK1/2 hyperphosphorylation, which has been shown in numerous cancers to induce uPAR. Treatment of the BRAFV600E-positive PTC cell line, BCPAP, with the MEK/ERK inhibitor U0126 reduced uPAR RNA levels by 90%. siRNA-mediated down-regulation of uPAR in BCPAP cells resulted in drastically reduced proliferation rates and decreased clonigenic survival, as well as demonstrated senescence-associated nuclear morphology and induction of β-galactosidase activity. uPAR-knockdown BCPAP cells also displayed greatly reduced migration and invasion rates, as well as a complete loss of the cells’ plasminogen-enhanced invasiveness. Additionally, uPAR down-regulation lead to greatly decreased activity in the focal adhesion kinase (FAK)/phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, as well as a modest reduction in ERK1/2 signaling (which remained constitutively active secondary to BRAFV600E activation), which suggests the existence of a uPAR signaling feedback loop capable of affecting the various phenotypic changes exhibited by uPAR-knockdown cells. Taken together, these data provide new evidence of a novel role for uPAR induction as a central component in PTC pathogenesis, and highlight the potential of uPAR as a therapeutic target.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1406. doi:10.1158/1538-7445.AM2011-1406
Abstract 1407: Mitogen-activated protein kinase kinase 4 (MEK4) is a key regulator of prostate cancer progression
Authors: Pavese Janet M. , Ogden Irene M. , Huang Xiaoke , Xu Li , Bergan Raymond C. 
Published: June 2012

Abstract
Mitogen-activated protein kinase kinase 4 (MEK4) is a dual-specificity kinase that has been implicated in cancer progression in multiple cancer types, including prostate cancer (PCa). MEK4 is upregulated in invasive PCa lesions in human tissue. We hypothesize that increased MEK4 promotes PCa invasion and metastasis. Our group has created PC3-M cells stably transfected with either constitutively-active or increased levels of wild-type MEK4. In a Matrigel Boyden chamber assay, constitutively-active or wild-type MEK4 was shown to increase PCa invasion. Cancer cell invasion requires the coupling of cell migration with increased production of proteases. We hypothesized that MEK4 promoted invasion via production of proteases, but not via cell migration. Using an uncoated boyden chamber, MEK4 was shown not to affect migration. Using quantitative real time polymerase chain reaction (qRT/PCR), we went on to demonstrate that MEK4 increased MMP-2 and MMP-9 transcript expression, but did not affect MMP-10 expression. In addition to these studies, we have also looked at the effect of increased or constitutively-active MEK4 on an orthotopic mouse model of PCa. In this model, PCa cells are injected into the prostates of nude mice and tumor size, circulating tumor cells, and lung metastasis are quantified. Preliminary data shows that constitutively-active MEK4 causes an increase in primary tumor size as well as an increase in circulating tumor cells in both the blood and the bone marrow. In summary, we demonstrated that chronic high expression of MEK4 increases human PCa invasion, that this is not due to increased migration, but is associated with increases in MMP-2 and MMP-9. Further, constitutively-active MEK4 appears to have different biological effects than high levels of wild type MEK4 in vivo. Ongoing studies are evaluating the effect of wild type MEK4 and of constitutively-active MEK4 on the formation of distant soft tissue metastasis in the above murine model. In related studies we are seeking to identify downstream proteins critical for MEK4's effects on cell invasion and metastasis both in vitro and in vivo. We are also seeking to examine the effects of sustained MEK4 knockdown on PCa invasion and metastasis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1407. doi:10.1158/1538-7445.AM2011-1407
Abstract 1408A: Estrogen can stimulate cholangiocarcinoma cells proliferation and invasion and associate with poor prognosis
Authors: Thuwajit Peti , Hunsawong Taweewun , Thuwajit Chanitra 
Published: June 2012

Abstract
Cholangiocarcinoma is defined as a cancer arising from bile duct epithelial cell. The prevalence of cholangiocarcinoma is low among worldwide, however it was raised each year. Moreover, this kind of cancer is endemic in Thailand which associated with liver fluke infection, Opisthorchis viverrini. In Thailand, the prevalence of cholangiocarcinoma was about 20-time higher than in western country and may be more than 400-time in endemic area (northeastern part). Cholangiocarcinoma has poor prognosis with low 5-year survival rate due to its high metastasis rate which caused inadequate surgery while chemotherapy and radiotherapy are resisted. It is a type of chronic liver disease with altered estrogen metabolizing enzyme that could leading to the accumulation of estrogen in plasma. Estrogen was known as a promoting factor in progression of some cancer, eg. breast cancer and endometrial cancer. Our finding indicated the increasing of serum estrogen level in male cholangiocarcinoma patients and correlated with serum alkaline phosphatase and bilirubin and inverse correlated with albumin. The high level of serum estrogen could be determined as poor prognostic factor for survival of cholangiocarcinoma patients with statistically significant. In vitro studies demonstrated the effect of estrogen on cell proliferation and invasion of cholangiocarcinoma cell lines. Real time proliferative assay indicated the growth stimulated effect of estrogen on 4 cholangiocaricinoma cell lines (KKU-100, KKU-M055, KKU-M156 and KKU-M213) in dose dependent manner up to 10 nM. Results from in vitro invasion assay showed the effect of estrogen on cholangiocarcinoma cell invasion with highest effect at concentration 1 nM and this effect could be inhibited by tamoxifen. Metastasis genes expression of KKU-M213 cholangiocarcinoma cell induced by estrogen was measured by RT2 ProlifilerTM PCR array system. Total 84 metastasis genes expression were compared with non-induced cell, 24 genes showed change in expression level more than twice which were 11 genes increased and 13 genes decreased. The pathway of estrogen induced metastasis genes in cholangiocarcinoma cells should be analyzed. The results should indicate the mechanism and control of cholangiocarcinoma invasion and metastasis, which may be introduced to the new therapeutic guideline.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1408A. doi:10.1158/1538-7445.AM2011-1408A
Abstract 1411: Overexpression of IFITM1 is associated with gastric cancer and its silencing inhibits migratory and invasive potential of tumor cells
Authors: Lee Jieun , Song Naaleum , Goh Sung-Ho , Choi Il Ju , Jeong Jin Sook , Lee Yeon-Su 
Published: June 2012

Abstract
Gastric cancer is the most common types of human cancer with an annual incidence of approximately 870,000 new cases worldwide (Crew K D, Neugut A I, Epidemiology of gastric cancer, World J Gastroenterol 2006;12(3):354-362). Despite its high prevalence, the risk factors and tumorigenesis of gastric cancer are not clearly identified. Consequently, the identification of the oncogene or tumour suppressor gene in gastric cancer has been the focus of many researches. In our effort to find gastric cancer related genes, we analysed the gene expression profiles in 30 pairs of gastric cancer patient samples (tumour and normal tissue) using microarrays and identified interferon-induced transmembrane protein 1 (IFITM1) as a highly up-regulated gene in tumor tissues. IFITM1, also known as 9-27 or Leu13, is a cell surface molecule and the IFN-inducible transmembrane protein family. However, there have been a few papers of IFITM1 explaining its function, and the role of IFITM1 in cancer is poorly understood. In the present study, we examined the roles of IFITM1 for gastric cancer and its function for tumoringenesis. Quantitative real-time PCR, western blot analysis and immunohistochemical staining were performed to confirm the cancer specific expression pattern of IFITM1. In various gastric cancer cell lines, IFITM1 mRNA expression level was highly up-regulated in comparison human mammary epithelial cell (HMEC). Furthermore, mRNA expression of IFITM1 was significantly up-regulated in cancer tissues than matching normal tissues. In addition, IFITM1 overexpression was observed in gastric adenocarcinoma by immunohistochemistry. Interestingly, cells which overexpressed IFITM1 exhibit an increased migration, invasion and wound healing potential. Consistently, IFITM1 knockdown cells by siRNA showed a decreased invasiveness. Our findings suggest that IFITM1 plays an important role for the migration, invasion and wound healing capacity of cancer cells and associated with progression of gastric cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1411. doi:10.1158/1538-7445.AM2011-1411
Abstract 1413: Hepatocyte growth factor activator inhibitor-2 inhibits prostate cancer cell migration and invasion
Authors: Wu Shang-Ru , Teng Chen-Hsin , Tsai Chin-Hsien , Tu Ya-Ting , Cheng Tai-Shan , Shyu Hsin-Yi , Ko Chun-Jung , Lan Shao-Wei , Huang Hsiang-Po , Lin Chen-Yong , Hsiao Pei-Wen , Lee Ming-Shyue 
Published: June 2012

Abstract
Dysregulation of proteolysis on cell surface has been strongly implicated in cancer cell migration and invasion. In this study, we delineated the role of hepatocyte growth factor activator inhibitor-2 (HAI-2) in prostate cancer cell migration and invasion within a human prostate cancer progression model, established by a serial of intraprostatic injections of prostate cancer cells and isolation of the invasive cells from nearby lymph nodes. The invasion capability of these cells was increased after the serial isolations. Interestingly, the expression of HAI-2 but not HAI-1 was dramatically decreased following the progression and concurrent with an increase of activated matriptase. Overexpression of HAI-2 reduced prostate cancer cell migration and invasion, at least in part due to its inhibitory role in matriptase. Following the orthotopic tumor growth in mice, the level of matriptase was increased while HAI-2 protein level was decreased. These results indicated that during the progression of human prostate cancer, HAI-2 expression was reduced, leading to constitutive matriptase activation, increased cell migration and invasion. Thus, HAI-2 exerted an inhibitory role in prostate cancer progression partly through inhibiting matripase activity. Imbalance between HAI-2 and matriptase may result in prostate tumor progression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1413. doi:10.1158/1538-7445.AM2011-1413
Abstract 1422: Abrogation of prostate cancer cell metastatic phenotype by cathepsin-L inhibition
Authors: Sudhan Dhivya R. , Siemann Dietmar W. 
Published: June 2012

Abstract
Prostate cancer is the most commonly diagnosed cancer in North America and the second leading cause of cancer death in men. Although highly curable in early stages, ∼90% of patients with advanced prostate cancer develop skeletal metastases; an occurrence that results in a substantial reduction in the quality of life and a drastic worsening of the prognosis. Tumor cells rely on proteolytic enzymes for successful establishment of metastases. Cathepsin-L (Cts-L) is a lysosomal endopeptidase of the papain super family of cysteine protease that is up regulated in a wide range of human cancers including prostate cancer. Cts-L over expression can enhance the invasive/metastatic potential of cancer cells through two distinct mechanisms: (i) degradative proteolysis of extracellular matrix and basement membrane components by secreted Cts-L and (ii) enhanced expression of genes involved in EMT and migration by nuclear Cts-L.
The goal of the present studies was to elucidate whether the administration of the specific small molecule CtsL inhibitor 3-bromophenyl-3-hydroxyphenyl-ketone thiosemicarbazone (KGP-94) could inhibit the metastatic phenotype in prostate cancer cells. PC-3 and its sublines PC-3-ML and PC-3-N which possess moderate, high, and low metastatic potential, respectively, were used. In response to treatment with 25uM of KGP-94, PC-3 and PC-3-ML showed a 45 and 55% decrease in migratory potential respectively as determined by transwell and wound healing assays. KGP-94 also significantly affected the invasive potential of PC-3 and PC-3-ML at 10uM and 25uM dose concentrations. These results occurred in the absence of cytotoxicity as determined using a clonogenic cell survival assay. Cell cycle analysis by flow cytometry did show that KGP-94 treatment induces a G1 arrest but this effect was insufficient to account for the pronounced inhibition of migration and invasion.In order to elucidate whether KGP-94 treatment affected nuclear Cts-L, presence of the nuclear isoform was validated in PC-3 cells through immunoblot analysis of nuclear extracts and confocal imaging. Nuclear Cts-L has been reported to induce epithelial to mesenchymal transition through increasing expression of Vimentin, N-Cadherin with concomitant suppression of E-Cadherin. However, quantitative PCR analysis failed to show an effect on the expression of these genes in response to KGP-94 treatment. These data therefore suggest that the abrogation of migratory and invasive potential observed in the prostate cancer models is a consequence of an inhibitory effect on secreted and not nuclear Cts-L.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1422. doi:10.1158/1538-7445.AM2011-1422
Abstract 1424: Cyclophilin A induces head and neck squamous cell carcinoma (HNSCC) invasion by its interaction to EMMPRIN/CD147
Authors: Suzuki Shinsuke , Takahashi Masafumi , Ishikawa Kazuo 
Published: June 2012

Abstract
Extracellular matrix (ECM) remodeling that is crucial in tumorigenesis involves proteolytic enzymes, primarily matrix metalloproteases (MMPs). The production of MMPs is stimulated by different factors, including extracellular matrix metalloprotease inducer (EMMPRIN/CD147). Over-expression of EMMPRIN, a member of the immunoglobulin super-family, promotes invasion, metastasis, growth and survival of malignant cells. Cyclophilin A (CypA) is a multifunction protein and promotes cancer progression in various cancer types. It has been reported CypA can interact and activate EMMPRIN, however the role of EMMPRIN-Cyp A interaction in oncogenicity is not fully understood in malignant cells including head and neck squamous cell carcinoma (HNSCC). In order to evaluate tumorigenicity that are induced by EMMPRIN-CypA interaction, EMMPRIN expressing HNSCC cell lines were stimulated with CypA. The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] dye assay revealed that HNSCC cell proliferation was increased, whereas cisplatin induced cell death was declined in the presence of CypA. In addition, CypA induced MMP-9 up-regulation was detected in culture medium by gelatin zymography. Moreover, increment of invaded cells through matrigel-coated membranes was found by CypA stimulation. Interestingly the elevated invasive potential was abrogated by EMMPRIN function blocking antibody. These findings suggest that CypA, by its interaction to EMMPRIN, might contribute to the HNSCC tumorigenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1424. doi:10.1158/1538-7445.AM2011-1424
Abstract 1428: Upregulation of IKBKE promotes glioma cell migration and invasion by phosphorylation of Snail
Authors: Guo Jianping , Huang Qiang , Shu Shaokun , Kim Donghwa , Brem Steven S. , Cheng Jin Q. 
Published: June 2012

Abstract
IKBKE is a member of IκB kinase (IKK) family. Previous studies have shown that IKBKE is an oncogene in breast and ovarian cancer. In this study, we demonstrate that IKBKE is frequently upregulated in human glioma and regulates cell invasion, a process that causes incurable surgery for glioma. Increase expression of IKBKE was detected in 7 of 11 glioma cell lines and 41 of 57 primary tumors examined, which closely correlates with high grade tumors and patient poor overall survival. Further, ectopic expression of IKBKE induces and knockdown of IKBKE decreases cell migration and invasion. Notably, E-cadherin protein and mRNA levels were inversely regulated by IKBKE. Moreover, we demonstrated that IKBKE directly binds and phosphorylates Snail at Ser-165. The phosphorylation of Snail induces its stability and nuclear translocation and represses E-cadherin expression. Taken together, these findings indicate that IKBKE could play a pivotal role in gliomagenesis and invasion.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1428. doi:10.1158/1538-7445.AM2011-1428
Abstract 1431: An optimized in vitro method to evaluate primary tumor cell invasion using optical imaging technology
Authors: Bockhorn Jessica , Chang Ya-Fang , Liu Huiping , Greene Geoffrey 
Published: June 2012

Abstract
The recent development of human-in-mouse tumor models has provided better representative working models to understand tumor initiation and progression than previous mouse tumor models or cell lines. However, it has not been feasible to use these models for high-throughput functional or therapeutic screening. Our aim was to establish a complementary in vitro culturing system for high-throughput functional studies or therapeutic screening of breast cancer stem cells (BCSCs). We hypothesize that with extracellular matrix and stromal cell support, three-dimensional (3D) cultures can support the survival and invasion of primary human tumors in vitro. We report here a new method to objectively evaluate and quantify invasion of primary breast cancer tumor cells using Transwells and bioluminescence imaging (BLI) technology. We optimized the adhesion and invasion conditions for these primary tumor cells. We also labeled cells using Luc2-EGFP or -tdTomato lentiviral vectors so that the signal of all invaded cells could be quantified using BLI or fluorescence imaging of the entire bottom chamber of the Transwell system. Our results demonstrate that stromal cells are not only necessary for the survival of the primary tumor cells but also facilitate their invasion in vitro. This work establishes a new method for screening candidate genes, miRNAs and compounds that regulate growth, survival, invasion and drug sensitivity of primary tumor cells, including both BCSCs and non-BCSCs.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1431. doi:10.1158/1538-7445.AM2011-1431