bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1486: Mda-9/Syntenin regulates integrin signaling by facilitating membrane translocation of ILK/PINCH1/α-parvin complex
Authors: Hwangbo Cheol , Park Juhee , Lee Jeong-Hyung 
Published: June 2012

Abstract
Integrin-linked kinase (ILK), PINCH1 and α-parvin form a ternary complex that plays crucial roles in integrins signaling. We report here that mda-9/syntenin is essential for the assembly of integrin β1-ILK-PINCH1-α-parvin signaling complexes during adhesion to collagen-I (COL-1). Modulation of mda-9/syntenin expression affects COL-1-induced activation of protein kinase B (PKB/Akt). mda-9/Syntenin associates with ILK and this association is increased at the plasma membrane in response to COL-1. mda-9/Syntenin regulates COL-1-induced association between ILK and PKB/Akt, and plasma membrane targeting of ILK-PKB/Akt, suggesting that mda-9/syntenin modulates the plasma membrane targeting of PKB/Akt via ILK. Strikingly, inhibition of mda-9/syntenin impairs COL-1-induced plasma membrane translocation of ILK-PINCH1-α-parvin complex and the assembly of integrin β1-ILK-PINCH1-α-parvin signaling complexes. Consistently, inhibition of mda-9/syntenin blocks the COL-1-induced reorganization of actin cytoskeleton and cell migration, as well as activation of Rac1 and ERK1/21/2. Thus, our study defines the role of mda-9/syntenin in COL-1-induced integrin signaling and describes new mechanism of mda-9/syntenin for the regulation of cell migration.
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 1486. doi:10.1158/1538-7445.AM2011-1486
Abstract 1493: Tumor-associated soluble uPAR enhances endothelial cell migration by staffing into lipid rafts
Authors: Chetty Chandramu , Lakka Sajani S. , Bhoopathi Praveen , Ponnala Shivani , Rao Jasti S. 
Published: June 2012

Abstract
The expression of urokinase plasminogen activator receptor (uPAR), a heavily glycosylated glycosyl-phosphatidylinositol (GPI)-anchored cell surface receptor, induces cell migration, and its expression correlates with the malignant phenotype of various cancers. The soluble form of uPAR (s-uPAR), which is found in the circulation of cancer patients, is associated with tumor malignancy and serves as a prognostic marker for various cancers. As such, in the current study, we analyzed the effect of s-uPAR from glioblastoma tumor cell conditioned medium (TCM) on endothelial cell migration. Here, we present evidence that s-uPAR from tumor cells augments migration and invasion on vitronectin and fibronectin matrices of human umbilical vein endothelial cells (HUVEC). The membrane fraction of HUVEC, which were cultured on TCM, had increased amounts of s-uPAR recruited into the membranes of endothelial cells. Co-localization studies for GM1 ganglioside receptor (a lipid raft marker) and uPAR further demonstrated s-uPAR recruitment into lipid rafts of HUVEC. Further, western blot analysis for uPAR in lipid raft fractions from HUVEC cells grown on TCM confirmed s-uPAR recruiting onto HUVEC cell membranes. Moreover, the addition of functional blocking uPAR antibodies to TCM mitigated s-uPAR-enhanced HUVEC migration and invasion. Our data suggest that s-uPAR from tumor cells might be involved in the recruitment of endothelial cells in 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 1493. doi:10.1158/1538-7445.AM2011-1493
Abstract 1496: Proteolytic regulation of the Wnt/PCP pathway in cancer
Authors: Golubkov Vladislav , Prigozhina Natalie , Cieplak Piotr , Aleshin Alexander , Chekanov Alexey , Chernov Andrei , Zhang Danhua , Zhu Wenhong , Motamedchaboki Khatereh , Dong P. Duc , Strongin Alex 
Published: June 2012

Abstract
The non-canonical Wnt signaling pathway regulates planar cell polarity (PCP) and directed cell motility in processes as diverse as embryogenesis and cancer cell invasion. Here, we establish that the protein tyrosine kinase-7 (PTK7), an essential component of the Wnt/PCP pathway, strongly inhibits cancer cell invasion by reorganizing the actin cytoskeleton and altering actomyosin contraction. We also demonstrate that the pro-invasive membrane type-1 matrix metalloproteinase (MT1-MMP) functions as a principal sheddase of PTK7 and reverses its inhibition of cell invasion. MT1-MMP directly cleaves the PKP621↓LI sequence localized in an exposed region of the seventh Ig-like domain, generating an N-terminal, soluble PTK7 species (sPTK7) that interacts with membrane PTK7 in a dominant-negative fashion. Protease activity was reciprocally correlated with levels of PTK7 in several cell types and during zebrafish embryogenesis. Reduced PTK7 levels were observed in breast tumours compared to normal breast tissue. Conceptually, our data suggest that the Wnt/PCP pathway converges with pericellular proteolysis to regulate cell motility in normal development and cancer. Further insight into MT1-MMP regulation of Wnt/PCP may promote understanding of directional cell motility in embryogenesis and cancer and lead to identification of therapeutics to treat PCP-related developmental disorders and malignancy.
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 1496. doi:10.1158/1538-7445.AM2011-1496
Abstract 1501: Prostate-specific antigen cleaves nidogen-1
Authors: Mattsson Johanna , Ravela Suvi , Stenman Ulf-Håkan , Koistinen Hannu 
Published: June 2012

Abstract
Prostate-specific antigen (PSA or kallikrein-related peptidase 3, KLK3) is a chymotrypsin-like serine protease expressed in the prostate and secreted into seminal fluid. Several studies have demonstrated that PSA exerts anti-angiogenic activity in vitro and in vivo. Using a human umbilical vein endothelial cell (HUVEC) tube formation model, where the cells were grown on Matrigel™ basement membrane preparation, we recently showed that the enzymatic activity of PSA is essential for its anti-angiogenic function. Previously, PSA has been shown to cleave components of extracellular matrix (ECM), e.g., laminin and fibronectin, as well as unidentified proteins in Matrigel™. Proteolytic products of some ECM proteins, such as collagen XVIII-fragment endostatin, are known to be anti-angiogenic. Cleavage of ECM is also crucial for cancer cell invasion. We studied the PSA-generated protein fragments derived from Matrigel™ and aimed to characterize their anti-angiogenic activity.
PSA was purified from seminal fluid and incubated with Matrigel™ for 24 h at 37°C. The resulting proteolytic fragments were analyzed by SDS-PAGE and mass spectrometry. Recombinant human nidogen-1 (also known as entactin) was incubated with PSA for 18 h at 37°C and the fragments were analyzed by SDS-PAGE followed by silver staining. The effect of nidogen-1 fragments was studied in the HUVEC tube formation model.
We found that PSA cleaves nidogen-1 in Matrigel™. This was confirmed by using recombinant nidogen-1. The nidogen-1 fragments, however, did not have any anti-angiogenic effect on HUVECs in the tube formation model.
We conclude that the cleavage of nidogen-1 by PSA may lead to disruption of basement membrane structure and, thus, may inhibit HUVEC tube formation as well as facilitate cancer cell invasion. The nidogen-1 fragments per se do not mediate the anti-angiogenic function of PSA.
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 1501. doi:10.1158/1538-7445.AM2011-1501
Abstract 1503: Anticancer effects of a nutrient mixture in human melanoma cells A2058: Inhibition of cell proliferation, MMP expression, invasion and apoptosis
Authors: Roomi M. Waheed , Siddiqui Samee , Roomi Nusrath , Niedzwiecki Aleksandra , Rath Matthias 
Published: June 2012

Abstract
Introduction: Melanoma, an extremely aggressive cancer, causes the majority of skin cancer-related deaths, secondary to metastasis to other organs of the body, such as lymph nodes, lungs, liver, brain or bone. Currently, there are no viable treatments for melanoma. We investigated the effect of a specific mixture (PB) of quercetin, cruciferex, curcumin, green tea extract and resveratrol on human melanoma cell line A2058 for viability, MMP expression, invasion, apoptosis and cell morphology.
Materials and Methods: Melanoma cells A2058 (ATCC), were maintained in DMEM culture, supplemented with 10% FBS and antibiotics in 24-well tissue plates. At near confluence, cells were treated with PB at 0, 10, 25, 50, 75 and 100 mcg/mL concentration in triplicate at each dose. Cells were also treated with PMA (100 ng/mL) for MMP-9 induction. Cell proliferation was assessed by MTT assay, MMPs by zymography, invasion through Matrigel, apoptosis using green caspase detection, and morphology by H&E staining.
Results: PB inhibited proliferation of melanoma cells A2058 by 45% at 10 mcg/mL and 80% at 25-100 mcg/mL concentration, and inhibited the secretion of both MMP-2 and MMP-9 in a dose dependent manner with total inhibition at 50 mcg/mL concentration. Invasion through Matrigel was inhibited by 65% at 10 mcg/mL and 100% at 25 mcg/mL, respectively. PB also induced apoptosis in a dose-dependent fashion. H&E staining showed slight morphological changes at higher concentrations.
Conclusions: In conclusion, PB significantly inhibited melanoma cell growth, invasion through Matrigel, MMP-2 and -9 expression and apoptosis, important parameters for cancer prevention, suggesting PB as a potential effective treatment of melanoma.
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 1503. doi:10.1158/1538-7445.AM2011-1503
Abstract 1511: Macrophage aggressiveness in the lung tumor microenvironment
Authors: Quinton Ryan J. , Griffin David R. , Alegre Melissa M. , Robison Richard A. , O'Neill Kim L. 
Published: June 2012

Abstract
Macrophages are highly versatile phagocytes active in multiple roles in the immune system of vertebrates. However, within the tumor microenvironment, macrophages initiate and are exposed to a variety of cell signals. Some of these signals are involved in tumor growth, angiogenesis, and metastasis, and have been shown to alter macrophage function. These tumor associated macrophages display characteristics that indicate polarization from M1 to M2 phenotypes, and have been shown to promote angiogenesis and metastasis in cancer patients. In addition, clinical trials have shown that a high macrophage count in breast cancer patients is associated with a poor prognosis. We hypothesize that the engulfment ability and aggressiveness of macrophages incubated with lung cancer cells will be down regulated. Human mononuclear phagocytotic U937 cells were differentiated to macrophages by exposure to phorbol-12-myristate-13-acetate (PMA). These cells were then marked with APC fluorochrome dye for identification, and phagocytic activity was measured using PE conjugated fluorescent beads. Macrophages were incubated with two lung cancer cell lines (A549, H460) for various times and phagocytic indices were quantified using flow cytometry. Preliminary results indicated no change in phagocytic activity after 1 hour of exposure, and a 15% down regulation of overall engulfment after 24 hours of contact. These results were compared to cells incubated with non-cancerous lymphocytes, where there was no change in overall phagocytic activity. These data also indicated that the majority of normal macrophages were highly aggressive (engulfing 3 or more beads when analyzed by flow cytometry), but macrophages that were incubated with cancer cell lines experienced a statistically significant down regulation in aggressiveness, where the number of macrophages which engulfed 3 or more beads was reduced by 30% (p = 0.044). These findings indicate that exposure of U937-derived macrophages to lung cancer cell lines resulted in a possible shift towards the M2 phenotype.
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 1511. doi:10.1158/1538-7445.AM2011-1511
Abstract 1513: Mesenchymal stromal cells enhance the malignant potential of human colorectal cancer cells by inducing epithelial to mesenchymal transition-related phenomena
Authors: Mele Valentina , Muraro Manuele Giuseppe , Calabrese Diego , Giovenzana Chiara , Heberer Michael , Bocelli-Tyndall Chiara , Terracciano Luigi , Spagnoli Giulio Cesare , Iezzi Giandomenica 
Published: June 2012

Abstract
Background: Mesenchymal stromal cells (MSCs) are recruited to primary and metastatic sites of several tumour types, including colorectal cancer (CRC), and might contribute to tumour progression. The actual role played by MSCs and the mechanisms underlying MSC-tumour interactions remain to be clarified. We investigated the effects of human bone-marrow-derived MSCs (BM-MSCs) on CRC, in vitro and in vivo.
Material and methods: Human established CRC cell lines were cultured in the presence or absence of BM-MSCs, in direct contact or in transwell plates. After a five day culture, tumour cell proliferation was assessed by differential cell counts, surface molecule expression was analyzed by flow cytometry, and production of soluble factors in culture supernatants was measured by Raybio antibody array® and ELISA. Tumour cells, sorted upon co-culture by flow cytometry, were evaluated for the expression of epithelial to mesenchymal transition (EMT)-related genes by quantitative PCR and for in vitro invasiveness, by chemoinvasion assay. Furthermore, their tumorigenicity was assessed upon injection in NOD/SCID mice and developing tumours were analyzed by immunofluorescence.
Results: MSCs significantly increased tumour cell proliferation and decreased CD44 expression, independently of cell-to-cell contact. Analysis of co-culture supernatants revealed higher amounts of IL-6, MCP-1, RANTES and Angiogenin, in comparison to supernatants derived from single cultures. Moreover increased expression of several EMT-related genes, including SNAI2, TWIST, N-Cadherin, was detected on CRC cells sorted upon co-culture as compared with controls. Importantly, CRC cells co-cultured with MSCs showed higher invasive behaviour in vitro, than CRC cells cultured alone. No significant changes were observed in tumorigenicity. However, tumours originated from tumour cells co-cultured with MSCs showed a significantly higher vessel density as compared to controls.
Conclusions: MSCs reduce adhesiveness, induce expression of EMT-related genes and increase proliferation, invasiveness and angiogenic potential of CRC cells. These effects might contribute to CRC progression and spreading.
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 1513. doi:10.1158/1538-7445.AM2011-1513
Abstract 1522: Spheroid formation causes a decrease in ovarian cancer cell growth rate that persists through dissociation and growth as a monolayer
Authors: Pease Jillian C. , Tirnauer Jennifer S. 
Published: June 2012

Abstract
Ovarian cancer has the highest mortality of all cancers of the female reproductive system. It accounts for three percent of all cancers in women and is the fifth leading cause of cancer-related death among women in the United States. Ovarian cancer cells can metastasize to the uterus, fallopian tubes, and pelvis tissues as well as to other organs. Even with optimal treatment there is a high probability that the cancer will recur, suggesting that current treatments are not successful in eliminating all of the ovarian cancer cells. This may be a result of a protective mechanism of the ovarian cancer cells. Spheroids are large collections of cancer cells that adhere tightly to each other rather than spreading out across an underlying basement membrane. They have been observed in ovarian cancer both in vivo and in ovarian cancer cell lines. Spheroids have been shown to play a role in the metastasis of ovarian cancer cells and have also been shown to be drug resistant. It is our hypothesis that spheroid formation results in epigenetic changes promoting the survival of ovarian cancer cells. Our data suggests that spheroid growth causes the growth rate of ovarian cancer cells to decrease and remain decreased following the transition from spheroids back to monolayer culture. Furthermore, serial passaging of ovarian cancer spheroids results in an increase in resistance to cytotoxic drugs. Since the decrease in growth rate appears to be persistent after spheroid culture it is likely the result of epigenetic modifications that occur during spheroid formation. These epigenetic changes, currently being studied, could become potential drug targets, as new treatments are developed to not only kill ovarian cancer cells but also prevent spheroid formation.
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 1522. doi:10.1158/1538-7445.AM2011-1522
Abstract 1527: Hepatocyte growth factor modulates adhesion of ovarian cancer cells to the peritoneum mesothelium through p70 S6 kinase
Authors: Ip Carman K.M , Yung Susan , Chan Tak-Mao , Wong Alice S.T. 
Published: June 2012

Abstract
Ovarian cancer has the highest mortality of all gynecological cancers. These deaths are mainly due to the highly metastatic characteristic with already widespread peritoneal dissemination and malignant ascites at the time of diagnosis. However the molecular mechanisms that regulate ovarian cancer progression are poorly understood. A key step in this process is the adhesion of ovarian cancer cells to the peritoneal mesothelium. Hepatocyte growth factor (HGF) is present at high concentrations in ovarian cancer ascitic fluid. We show here a role for HGF signaling in the regulation of the peritoneal adhesion of ovarian cancer cells. HGF increased binding of ovarian cancer cells to peritoneal extracellular matrix (ECM) proteins fibronectin and laminin and their receptors α5, α6, and β1 integrin expression. Blockade of HGF resulted in reduced attachment of ovarian cancer cells to these ECM proteins, with a concomitant reduction of α5, α6, and β1 integrin expression, confirming that the effect was HGF specific. Similarly, the peritoneal ECM adhesion could be reversed by neutralizing antibodies to α5, α6, and β1 integrin. The adhesive phenotype and integrin expression activated by HGF could be blocked by specific inhibition of p70 S6 kinase (p70S6K) using short hairpin RNA or small molecule inhibitor, suggesting that HGF transmits the signal through p70S6K. Importantly, it also inhibited adhesion to primary human peritoneal mesothelial cells. These results identify a potential novel mechanism for HGF-induced peritoneal adhesion, which is mediated through p70S6K through regulation of α5, α6, and β1 integrin (This work is supported by the Hong Kong Research Grants Council Grant HKU7599/05M to A.S.T.W.).
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 1527. doi:10.1158/1538-7445.AM2011-1527
Abstract 1529: Knockdown of cathepsin B and uPAR inhibits CD151 and α3β1 integrin-mediated cell adhesion in glioma
Authors: Malla Rama Rao , Gopinath Sreelatha , Alapati Kiranmai , Gondi Christopher S. , Rao Jasti S. 
Published: June 2012

Abstract
Glioma is a highly complex brain tumor characterized by deregulation of proteins and genes that play important roles in tumor metastasis. CD151, a member of the tetraspanin family of proteins, tightly associates with integrins and accelerates cell adhesion as a modulator of actin cytoskeletal reorganization. Cathepsin B and uPAR are both overexpressed in gliomas and postulated to play central roles in the mediation of glioma metastasis. In the present study, cathepsin B and uPAR were downregulated in U251 and 4910 glioma cells using siRNA plasmid constructs. We evaluated the involvement of CD151 and its associated signaling molecules in adhesion potential. Immunoblot analysis revealed efficient downregulation of cathepsin B and uPAR after siRNA treatments. In addition, siRNA treatments significantly inhibited glioma cell adhesion to laminin as compared to other extracellular matrix proteins. Brain glioma tissue array analysis revealed the expression of CD151 in several tumor samples when compared with normal brain tissue. Further, treatment of glioma cells with cathepsin B and uPAR siRNA led to the downregulation of CD151 and laminin-binding integrins, α3 and β1. Co-localization and immunoprecipitation experiments revealed that downregulation of cathepsin B and uPAR decreased the interaction of CD151 with uPAR/cathepsin B. Transcriptional suppression of CD151 and α3 and β1 integrins using siRNA significantly decreased glioma cell adhesion to laminin. In addition, downregulation of cathepsin B, uPAR, CD151, α3 and β1 significantly decreased the expression of N-cadherin and β-catenin. Studies on the downstream signaling cascade of uPAR/CD151 have shown that phosphorylation of SRC, FAK and Paxillin were reduced with knockdown of cathepsin B, uPAR and CD151. Treatment with the bicistronic construct reduced CD151, α3β1 integrin, N-cadherin and β-catenin expression levels in pre-established glioma tumors in nude mice as well as in tissue lysates. In conclusion, our results show that downregulation of cathespin B and uPAR alone and in combination inhibit glioma cell adhesion by downregulating CD151 and its associated signaling molecules in vitro and in vivo. This study may be useful in dissecting the pathways involved in tumor cell adhesion and for the identification of novel target proteins for therapeutic intervention of gliomas.
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 1529. doi:10.1158/1538-7445.AM2011-1529