bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1384: Estrogen receptor beta inhibits migration and invasion of breast cancer cells by regulating E-cadherin levels
Authors: Thomas Christoforos , Rajapaksa Gayani , Nikolos Fotis , Gustafsson Jan-Ake 
Published: June 2012

Abstract
Estrogen receptor beta (ERβ) mediates the effects of estrogens in a variety of human tissues including the mammary gland and regulates biological processes involved in initiation, progression and metastasis of breast cancer such as cell proliferation and migration. Although induction in cell-cell adhesion has been shown to be involved in the ERβ-mediated inhibition of cell migration, the molecular mechanism has not been fully elucidated. Here we show that induction in the expression of ERβ alters the morphology of the metastatic MDA-MB-231breast cancer cells by inducing cell-cell contact and inhibits migration and invasion. This correlates with an ERβ-mediated induction in the expression of the epithelial marker E-cadherin and downregulation of mesenchymal markers vimentin and N-cadherin. We found that the ERβ-mediated increase in the expression of E-cadherin involves an induction in the levels of miR-200 and a concomitant downregulation of its target component and transcriptional repressor of E-cadherin, ZEB1. These data suggest that ERβ through inhibiting migration and invasion in breast cancer cells may have a role in the clinical intervention of metastatic breast 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 1384. doi:10.1158/1538-7445.AM2011-1384
Abstract 1387: WISP-1 increases MMP-2 expression and cell motility in human chondrosarcoma cells
Authors: Chiang Yi-Chun , Tang Chih-Hsin , Tan Tzu-Wei 
Published: June 2012

Abstract
Chondrosarcoma is a type of highly malignant tumor with a potent capacity to invade locally and cause distant metastasis. Chondrosarcoma shows a predilection for metastasis to the lungs. WISP-1 is a cysteine-rich protein that belongs to the CCN (Cyr61, CTGF, Nov) family of matricellular proteins. However, the effect of WISP-1 on migration activity in human chondrosarcoma cells is mostly unknown. Here we found that WISP-1 increased the migration and expression of matrix metalloproteinase (MMP)-2 in human chondrosarcoma cells (JJ012 cells). We also found that human chondrosarcoma tissues had significant expression of the WISP-1 which was higher than that in normal cartilage. α5β1 monoclonal antibody and MAPK kinase (MEK) inhibitors (PD98059 and U0126) inhibited the WISP-1-induced increase of the migration and MMP-2 up-regulation of chondrosarcoma cells. WISP-1 stimulation increased the phosphorylation of focal adhesion kinase (FAK), MEK and extracellular signal-regulated kinase (ERK). In addition, NF-κB inhibitors also suppressed the cell migration and MMP-2 expression enhanced by WISP-1. Moreover, WISP-1 increased NF-κB luciferase activity and binding of p65 to the NF-κB element on the MMP-2 promoter. Taken together, our results indicated that WISP-1 enhances the migration of chondrosarcoma cells by increasing MMP-2 expression through the α5β1 integrin receptor, FAK, MEK, ERK, p65 and NF-κB signal transduction pathway.
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 1387. doi:10.1158/1538-7445.AM2011-1387
Abstract 1388: Metastatic potential of B16 melanoma subclones indicated by cell stiffness measured by atomic force microscopy (AFM)
Authors: Suganuma Masami , Watanabe Tatsuro , Takahashi Atsushi , Fujiki Hirota 
Published: June 2012

Abstract
To investigate a new parameter for measuring the metastatic potential of cancer cells, we conducted nanomechanical analysis using atomic force microscopy (AFM). AFM, a probe microscope, has the advantage of measuring cell stiffness (elasticity) in physiological conditions without any pretreatment. Since cancer cells are softer than normal cells, the cell stiffness measured by AFM can be utilized as a new cancer diagnostic marker. Experimentally, we examined whether cell stiffness might reflect the metastatic potential of cancer cells using three subclones (B16-F10, B16-BL6, and B16-F1) of B16 melanoma cells. Migration potential was first determined by Transwell assay: B16-F10 and B16-BL6 cells showed 3- and 2- times more migrated cells into reverse sides of filter, at 5 μg/ml concentrations of fibronectin, than did B16-F1 cells. This indicates that B16-F10, B16-BL6, and B16-F1 cells have metastatic potential in the order of high, intermediate, and poor, respectively. AFM measurement clearly shows significant differences in cell stiffness of three B16 subclones, while the morphology and growth rate of these subclones are almost the same. Median values of Young’ modulus with B16-F10, B16-BL6, and B16-F1 cells were 395.12 Pa, 771.13 Pa, and 868.45 Pa, respectively. The results showed that highly metastatic B16-F10 cells are least stiff, suggesting that cell stiffness (Young's modulus) is directly associated with metastatic potential. Furthermore, we found that treatment with green tea catechin EGCG increased the cell stiffness of B16-F10 cells to greater than that of non-treated cells, and it also inhibited of cell migration in Transwell assay. Moreover, an inactive catechin, EC, did not have any effect on cell stiffness or cell migration. The results with EGCG strongly support our previous finding that EGCG in drinking water inhibits the metastasis of B16-F10 cells into the lungs of C57/BL6 mice. We have present for the first time evidence that the cell stiffness, as determined by AFM, is a useful biomarker for predicting metastatic potential and developing new preventive agents against metastasis. We discuss the significance of this mechanical and biochemical property (cell stiffness) in 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 1388. doi:10.1158/1538-7445.AM2011-1388
Abstract 1391: Simultaneous knockdown of MMP-9 and uPAR/cathepsin B retards α9β1 integrin-mediated cell migration via SSAT and potassium channel pathway in glioma xenografts
Authors: Veeravalli Krishna Kumar , Ponnala Shivani , Chetty Chandramu , Rao Jasti S. 
Published: June 2012

Abstract
The α9β1 integrin accelerates cell migration through the binding of α9 cytoplasmic domain to spermidine/spermine-N1-acetyltransferase (SSAT), which catalyzes the catabolism of higher order polyamines, spermidine and spermine, to the lower order polyamine, putrescine. Our recent studies have clearly demonstrated the role of α9β1 integrin in MMP-9, uPAR and cathepsin B-mediated cell migration in glioma xenograft cells (4910 and 5310). In the present study, we aimed to investigate the underlying mechanisms through which MMP-9 and uPAR/cathepsin B knockdown inhibits α9β1 integrin-mediated migration in glioma xenograft cells. Western blot, RT-PCR and immunofluorescence analyses revealed downregulation of SSAT levels both at the mRNA and protein levels by siRNA-mediated simultaneous knockdown of MMP-9 and uPAR/cathepsin B. In addition, we noted a prominent reduction in the expression of SSAT with MMP-9 and uPAR/cathepsin B knockdown in the tumor regions of 5310 injected nude mice brains. Co-localization of α9 integrin with kir4.2, an inward rectifier potassium channel, was observed in both 4910 and 5310 xenograft cells. However, MMP-9 and uPAR/cathepsin B knockdown in these cells prominently reduced the co-localization of α9 with kir4.2. Interestingly, MMP-9, uPAR and cathepsin B overexpression in these xenograft cells significantly elevated SSAT mRNA and protein levels. Further, the migratory potential of MMP-9/uPAR/cathepsin B overexpressed 4910 and 5310 cells was not affected by either glybenclamide or tertiapin-Q but instead was significantly inhibited by either barium or kir4.2 siRNA treatments. Taken together, our results from the present and earlier studies clearly demonstrate that α9β1 integrin-mediated cell migration utilizes SSAT and kir4.2 potassium channel pathway, and inhibition of the migratory potential of these glioma xenograft cells by simultaneous knockdown of MMP-9 and uPAR/cathepsin B could be attributed to the reduced SSAT levels and co-localization of α9 integrin with kir4.2 potassium channels. Based on these findings, we conclude that the simultaneous knockdown of MMP-9 and uPAR/cathepsin B retards SSAT and potassium channel pathway-mediated cell migration through the α9β1 integrin.
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 1391. doi:10.1158/1538-7445.AM2011-1391
Abstract 1393: CD44 has dual functions to enhance the hyaluronan-induced chemokinesis in cancer cells as an associated molecule of hyaluronidase2-mediated HA catabolism and a hyaluronan receptor for RhoGTPase activation
Authors: Harigaya Kenichi , Saito Teruyoshi , Azuma Kazuhiko , Umemiya Toshifumi , Toyoda Akihiro , Shida Yuki , Kitagawa Motoo 
Published: June 2012

Abstract
Major oncogenic signaling pathways are involved in the alteration of hyaluronan (HA) metabolism of cancer cells, such as Erb B, Wnt, TGF-β and p53 signalings. HA is a widely distributed extracellular matrix glycosaminoglycan and changes biological activities depending on its molecular sizes. Our recent study has shown that fragmented low molecular weight (LMW) HA (approximately 20 kDa) is an autocrine chemokinetic motility factor supported by the HA synthethase2-hyaluronidase2 / CD44 system on the plasma membrane of the cancer cells. In HeLaS3 cells, LMW-HA stimulation effectively enhanced cell spreading and random cell movement (chemokinesis) among different molecular sizes of HA (3, 23, 230, 940-kDa). Biochemically, LMW HA effectively provoked a RhoA activation, recurrent Cdc42 and Rac1 activation, and sustained phosphorylation of ERK1/2. Constrastly, 220 kDa HA did not enhance chemokinesis of HeLaS3 cells with similar activation profiles of Rac1 and ERK 1/2 except for the progressive decrease of Cdc42 and RhoA activation. The transfection of CD44 si-RNA to HeLaS3 cells abolished the enhanced chemokinesis with the remarkable decrease of Rho GTPase activation even in LMW HA stimulation. Accordingly, our study showed that CD44 has dual functions to enhance the HA-induced chemokinesis in cancer cells as an associated molecule of hyaluronidase2-mediated HA catabolism and a HA receptor for RhoGTPase activation.
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 1393. doi:10.1158/1538-7445.AM2011-1393
Abstract 1395: CD16+ dendritic cells (DC) promote squamous carcinoma cell (SCC) survival, and SCC affect DC phenotype and migration
Authors: Kurago Zoya B. , Ramanathapuram Lalitha 
Published: June 2012

Abstract
In the inflammatory mucosal microenvironment of head and neck squamous cell carcinoma (HNSCC), dendritic cells (DC) are prominent; they express CD16, and are usually in direct contact with tumor cells. Mucosal and inflammation-associated DC develop from monocytes, and monocyte-derived DC are used in HNSCC immunotherapy. However, beyond apoptotic tumor cell uptake and presentation of tumor antigens by DC, HNSCC cell interactions with DC are poorly understood. Using co-cultures of monocyte-derived DC and established HNSCC cell lines we found that carcinoma cells induced significant increases in CD16 expression on DC while promoting a CD1a+CD86dim immature phenotype, similar to that observed in HNSCC specimens. Moreover, HNSCC cells strongly affected DC migration, both steady-state and CCL21-induced. The effects of carcinoma cells on migration were donor-dependent, and CCL21-induced migration directly correlated with HNSCC-mediated effects on CCR7 and CD38 expression on DC. Most remarkably, the numbers of live detached HNSCC cells were orders of magnitude higher in DC-HNSCC co-cultures than in parallel HNSCC cell cultures without DC. This study provides a novel insight into the outcomes of DC-HNSCC interactions relevant to the tumor microenvironment.
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 1395. doi:10.1158/1538-7445.AM2011-1395
Abstract 1397: The effects of mevalonate pathway inhibitors on the motility and invasion of aggressive breast cancers
Authors: Kennedy Elizabeth J. , Bracken Eric A. , Van Wassenhove Lauren D. , Bao LiWei , Wu ZhiFen , Merajver Sofia D. 
Published: June 2012

Abstract
The mevalonate pathway is a metabolic pathway responsible for synthesizing prenyl (both farnesyl and geranylgeranyl) groups and activating small GTPase proteins through transfer of these groups by covalent modification. These GTPase proteins include RhoA, RhoC, Rac and Cdc42, which regulate the actin cytoskeleton during cellular migration and are over-expressed in many cancers. This project explores the effects of three mevalonate pathway inhibitors–zoledronic acid, atorvastatin and geranylgeranyl transferase inhibitor (GGTI)–on the single-cell motility, collective cell migration and invasion of an aggressive breast cancer line (MDA-MB-231) and an inflammatory breast cancer derived (IBC) line (SUM149). We are using MCF10A immortalized breast cells as our “normal-like” control. We hypothesize that these cancers rely on this pathway for cellular motility, invasion and the structure of the actin cytoskeleton more than normal epithelial cells.
We observed significant decreases in total quantities of Rac, RhoC and Cdc42 and a striking increase in RhoA upon treatment with each separate inhibitor, observed by western blot. The effect is much more potent with atorvastatin and GGTI, resulting in an almost complete loss of lamellipodia and filopodia. We assayed for invasion through 3D culture transwell chambers, individual cell motility using a bead motility assay and live-cell imaging, and collective cell migration using a wound healing assay. In general, all three drugs were highly effective at inhibiting both types of cell migration and invasion in MDA-MB-231 cells. While all drugs inhibited the collective cell migration of SUM149 cells, only GGTI additionally inhibited invasion and single cell migration. This result suggests that an approach targeting geranylgeranylation may be more effective for inhibition of IBC cells. Typically IBC tumors use collective cell migration mechanisms to metastasize, whereas MDA-MB-231 tumors metastasize through single-cell migration. Our results show that aggressive breast cancers heavily rely on the mevalonate pathway for cellular motility in comparison to normal epithelial cells, and that inhibitors of this pathway have significant potential to inhibit the metastatic properties of these two tumor types, given their mechanism of tissue invasion. We are continuing to study collective cell movement by assaying for cell-cell adhesion molecules upon treatment with our three inhibitors. In addition, we are studying the effects of these inhibitors on metastasis in vivo using xenograft mouse models and Her2Neu transgenic mouse models.
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 1397. doi:10.1158/1538-7445.AM2011-1397
Abstract 1399: CCN3 enhances migration and ICAM-1 upregulation via avb3 integrin, ILK, Akt, and NF-kB-dependent pathway in human prostate cancer cells
Authors: Chen Po-Chun , Tang Chih-Hsin , Cheng Hsu-Chen 
Published: June 2012

Abstract
Nephroblastoma overexpressed (NOV/CCN3), from the CCN gene family, is a secreted and matrix-associated protein, which is involved in many cellular functions such as growth, differentiation and adhesion. However, the effect of CCN3 in human prostate cancer is still unclear. Here, we found that CCN3 and intercellular adhesion molecule-1 (ICAM-1) expression level were related to cell migration ability in prostate cancer cells. In addition, CCN3 increased the migration and expression of ICAM-1 in human prostate cancer cells. RGD peptide, αvβ3 monoclonal antibody, integrin-linked kinase (ILK) and Akt inhibitors but not RAD peptide inhibited the CCN3-induced increase of the migration and ICAM-1 upregulation of prostate cancer cells. CCN3 stimulation activated the ILK/Akt/ NF-κB pathway. Moreover, CCN3 increased the binding of p65 to the NF-κB element on the ICAM-1 promoter. Finally, knock down of CCN3 expression markedly inhibited cell migration ability, tumor growth and bone destruction. Taken together, our results indicated that CCN3 enhances the migration of prostate cancer cells by increasing ICAM-1 expression through the αvβ3 integrin receptor/ ILK/ Akt and NF-κB signal transduction pathway. Therefore, CCN3 may be developed as alternate therapy of prostate cancer cells.
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 1399. doi:10.1158/1538-7445.AM2011-1399
Abstract 140: Tumor suppressor role of microRNA-1 in prostate cancer
Authors: Hudson Robert S. , Yi Ming , Esposito Dominic , Stephens Robert M. , Croce Carlo M. , Ambs Stefan 
Published: June 2012

Abstract
MicroRNAs (miRNA) are small non-coding RNAs that reduce the translation of target mRNAs via 3’ untranslated region (UTR) binding sites. MicroRNA-1 has been previously shown by genome-wide studies in our lab to be under-expressed in prostate cancer (PCa) tissues and lost in most of the NCI-60 cell lines. We hypothesize that miRNA-1 plays a role in the progression of PCa through tumor suppressor mechanisms. To explore this we used an integrated system biology approach by re-expressing miRNA-1 and studying its targetome by mRNA microarray analysis, miRNA target prediction, pathway analysis, and connectivity mapping. From these analyses we found that miRNA-1 down-regulated transcripts were significantly enriched for predicted targets and genes involved in cell cycle progression, mitosis, and DNA replication/repair. Following this we found evidence that miRNA-1 could increase the number of cells in S-phase while reducing mitotic cell numbers and the protein levels of genes required for S-phase progression including CHK1 and MCM7. Connectivity mapping of miRNA-1 expression profiles revealed that the effects of this miRNA overlap with histone deacetylase inhibitors like Vorinostat and Trichostain (TSA). Supporting this we found that miRNA-1 could be re-expressed when PCa cells were treated with epigenetic drugs such as 5-azadeoxycytidine and TSA. This could implicate a downstream role of miRNA-1 in these epigenetic mechanisms. Moreover, miRNA-1 expression increased radiation mediated levels and resolution of the DNA damage biomarker gamma-H2A.X, while reducing the clonogenic survival of PCa cells to radiation. This indicates that the loss of miRNA-1 could have clinical importance, by leading to an increase in the survivability of PCa cells to radiation therapy. Further, we found that several possible targets of miRNA-1 are actin binding genes that could play roles in both mitosis and migration. Using 3’UTR reporter assays we found that miRNA-1 directly targets several of these genes including, LASP-1, XPO6, NOTCH-3, FN1, MMD, and PTMA. Subsequently, epi-fluorescence microscopy revealed that miRNA-1 was capable of increasing F-actin levels and altering its organization in PCa cells. In conclusion, our findings indicate that miRNA-1 functions as a tumor suppressor in PCa by influencing cell cycle, the DNA damage response, and regulating actin related genes involved in mitosis and cell motility. These studies implicate a possible utility of miRNA-1 expression patterns in the therapeutic outcome of PCa patients.
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 140. doi:10.1158/1538-7445.AM2011-140
Abstract 1404: L1CAM in non-small-cell lung carcinoma
Authors: Hai Josephine , Zhu Chang-Qi , Der Sandy , Jurisica Igor , Tsao Ming-Sound 
Published: June 2012

Abstract
Background: Non-small-cell lung carcinoma (NSCLC) is the predominant type of lung cancer, accounting for 85% of all malignant lung tumors. Early stage (I-II) NSCLC is primarily treated by surgical resection with curative intent, but at least 50% of these patients will experience tumor recurrence and die from it. Recent clinical trials have demonstrated the survival benefit of post-surgery adjuvant chemotherapy in stage II and III patients, but its benefit in stage I remains controversial. Our group has previously reported a 15-gene mRNA expression profile that is predictive of patient prognosis and predictive of benefit from adjuvant chemotherapy by cisplatin and vinorelbine. We hypothesize that these genes may play important roles in malignant progression. One of these prognostic genes is L1CAM, a transmembrane protein. The role of L1CAM in the biology of NSCLC cells has not been clearly defined.
Methods: The expression of L1CAM was modified at both the RNA and protein levels in H460, H1264, H125, and H460SM cell lines using the lentiviral cDNA/shRNA system. Matrigel assay was used to assess invasion and cell migration by time-lapse wound-healing assay. Tumorigenicity was assessed by injection of modified cell lines into subcutaneous flank of immunodeficient mice.
Results: In vitro studies show that L1CAM expression promotes invasiveness and motility of NSCLC cell lines. In vivo studies demonstrate that knock-down of L1CAM expression reduces tumor growth in immunodeficient mice. Mechanistic studies on L1CAM function are ongoing and the results will be presented.
Conclusion: Considering the importance of migratory phenotype during metastasis, the results suggest that L1CAM contribute to malignant progression in NSCLC and may be a novel therapeutic target to treat this disease. (Supported by Canadian Cancer Society Research Institute grant #020527)
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 1404. doi:10.1158/1538-7445.AM2011-1404