bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2323: Inhibition of in vitro growth of human mesothelioma cells by CSPG4-specific monoclonal antibodies
Authors: Zeyana Rivera , Ferrone Soldano , Yang Haining , Wang Xinhui , Carbone Michele 
Published: February 2011

Abstract
The membrane bound chondroitin sulphate protidoglycan 4 (CSPG4), also known as high molecular weight-melanoma associated antigen (HMW-MAA), plays a role in tumor cell proliferation, growth and differentiation, as well as in angiogenesis and extracellular matrix remodeling. Contrary to the early reports which had described CSPG4 expression restricted to melanoma cells, this molecule is expressed by various types of malignant tumors. Because of its high expression on tumor cells, including cancer stem cells, and its restricted distribution in normal tissues, CSPG4 represents an attractive target for immunotherapy. The lack of effective conventional therapy and the paucity of suitable targets for immunotherapy in mesothelioma have prompted us to test whether CSPG4 is expressed by mesothelioma cells and mediates the anti-tumor activity of CSPG4-specific monoclonal antibodies (mAb). Immunohistochemical staining with mAb showed that CSPG4 was expressed on mesothelioma cells in 24 out of 40 MM biopsies with minimal expression on surrounding normal cells. Furthermore FACS analysis and western blots detected CSPG4 in all the 9 human MM cell lines tested and that the expression was induced on MM cells by their interactions with the extracellular matrix (ECM).
To test the sensitivity of MM cells to the anti-tumor activity of CSPG4-specific mAb, 3 MM cell lines were incubated with mAb TP41.2 (final concentration 10ug/ml) for up to 72hrs. Cell proliferation was determined by MTT assay. Cells incubated with normal mouse IgG antibodies were used as controls. Addition of mAb TP41.2 to cells already attached to plates had no detectable effect on their proliferation. On the other hand incubation of MM cells with mAb TP41.2 before seeding in plates markedly inhibited their growth. The effect was time-dependent. These results were observed in all 3 cell lines and each cell lines was tested 3 times. The data suggest that CSPG4 promotes MM cell growth by mediating their interactions with ECM. This conclusion is corroborated by the growth of CSPG4-positive MM cells in serum-free medium in plates coated with collagen I, collagen IV or fibronectin. Furthermore CSPG4-specific mAb decreased the expression of the angiogenic growth factors VEGF and HEY1, as determined by RT-PCR, in MM cells. These results suggest that it may be worthwhile to test the hypothesis that CSPG4-specific mAb-based immunotherapy may represent a viable approach for the treatment of MM.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2323.
Abstract 2324: The cell adhesion molecule L1-CAM is expressed in non-small cell lung cancer and is a prognostic marker for progression free survival
Authors: Tischler Verena M. , Hausladen Silke , Kristiansen Glen , Altevogt Peter , Moch Holger , Soltermann Alex 
Published: February 2011

Abstract
Aim: The cell adhesion molecule L1 (L1-CAM) is overexpressed in a variety of human cancers and is correlated to bad prognosis. So far only lung cancer cell lines have been tested for L1-CAM expression. Therefore, we aimed to evaluate the diagnostic and prognostic value of this molecule in non-small cell lung cancer (NSCLC) tissue.
Methods: We studied tumours of 509 surgically treated NSCLC patients, assembled on a tissue microarray. The cell membrane protein expression of L1-CAM was immunohistochemically determined and semi-quantitatively scored by two pathologists. Correlations of protein expression with clinico-pathologic parameters were calculated by chi-squared tests, overall survival by the Kaplan-Meier method.
Results: L1-CAM protein was overexpressed in 8.7% of the cases. Histological subtype analysis showed that of squamous cell carcinomas 12.9%, of adenosquamous carcinomas 33.3% and of adenocarcinomas 6.7% expressed high membranous L1-CAM. High L1-CAM protein expression was significantly correlated with higher grade, larger tumour size, higher stage and vessel infiltration but not with nodal state. High L1-CAM was significantly correlated with decreased overall survival on univariate analysis and found to be an independent prognostic factor on multivariate cox regression hazard models (including pT, pN and grade, all p-values &lt;0.05).
Conclusions: This is the first comprehensive study on L1-CAM expression in NSCLC. Particularly, epithelial expression of L1-CAM is significantly associated with shortened patient survival defining a subset of tumours with dismal prognosis.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2324.
Abstract 2332: Alphavbeta6 integrin, a downstream effector of TGFbeta, promotes prostate cancer osteolytic lesions
Authors: Li Jing , Akech Jacqueline , Pratap Jitesh , Wang Tao , FitzGerald Thomas J. , Jiang Zhong , Violette Shelia M. , Hussain Sadiq , Stein Gary S. , Lian Jane B. , Languino Lucia R. 
Published: February 2011

Abstract
Integrins and their extracellular matrix ligands are crucial regulators of cancer progression. We show in the present study that the alphaVbeta6 integrin is abundantly expressed in human bone metastasis and enhances metastatic bone disease, which occurs frequently in prostate and breast cancer patients.
Our analysis shows that alphaVbeta6 is upregulated in prostate cancer cells via a pro-metastatic signaling pathway mediated by TGFbeta and SMAD3. Given alphaVbeta6 ability to act as a downstream effector of TGFbeta, we tested the ability of alphaVbeta6 to mediate metastatic cancer growth in bone in vivo. We injected PC3 cells stably transfected with alphaVbeta6 in the tibiae of SCID mice. Intraosseous growth of these cells results in extensive osteolytic lesions. Micro-computed tomographic reconstruction of the various bone lesions demonstrates that expression of alphaVbeta6 promotes the appearance of osteolytic lesions beginning at 2 weeks after injection of the tumor cells, further progressing to massive trabecular and cortical bone loss by 4 and 8 weeks. In contrast, intraosseous growth of cells expressing alphaVbeta5, another alphaV containing integrin known to promote metastasis, does not result in osteolytic lesions at the same time intervals and causes woven bone deposition in the medullary cavity. Intraosseous tumors produced by intratibial injection of alphaVbeta6- or alphaVbeta5-expressing prostate cancer cells grew with indistinguishable kinetics, thus ruling out that the enhanced formation of osteolytic lesions mediated by alphaVbeta6 was simply due to accelerated tumor growth. Further analysis shows that alphaVbeta6 contributes to osteolytic lesions by selective upregulation of MMP2 levels in PC3 tumors in vivo, which, in contrast, is not observed in alphaVbeta5- PC3 tumors.
These findings show for the first time a mechanism that promotes alphaV integrin-mediated osteolysis in prostate cancer metastatic growth and suggest that the players involved are targets for future personalized therapies of prostate cancer.
Grant support: NIH R01 CA089720 (LRL).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2332.
Abstract 2333: Integrin β1 contributes to metastasis and prognosis of squamous cell carcinoma of the head and neck (HNSCC)
Authors: Wang Dongsheng , Wang Yuxiang , Amin A.r.m Ruhul , Su Ling , Muller Susan , Huang Donghai , Nannapaneni Sreenivas , Koenig Lydia , Chen Zhengjia , Pan Lin , Tighiouart Mourad , Shin Dong Moon , Chen Zhuo (Georgia) 
Published: February 2011

Abstract
Integrin β1 Contributes to Metastasis and Prognosis of Squamous Cell Carcinoma of the Head and Neck (HNSCC)
It is known that integrin β1 is involved in metastasis of various tumor types. We have previously demonstrated that integrin β1 not only serves as a potential biomarker, but also plays a role in metastasis of squamous cell carcinoma of the head and neck (HNSCC), evidently by increasing tumor cell invasion (AACR poster 09-Abstract-6472). To determine the significance of integrin β1 expression in the prognosis of HNSCC and the mechanism underlying the association of integrin β1 with metastatic disease, tissue specimens obtained from 207 patients with HNSCC (101 from patients with lymph node metastasis and 106 from patients without lymph node metastasis) were analyzed for integrin β1 expression, scored as percentage expression. Furthermore, integrin β1 was knocked down by shRNA in two HNSCC cell lines to investigate its effect on invasion and metastasis-related signal transduction pathways. Finally, an orthotopic xenograft metastatic model was utilized to verify the clinical and in vitro biological findings. Both univariate and multivariate statistical analysis showed that integrin β1 expression was significantly higher in metastatic primary tumors than in non-metastatic tumors (42.7% vs 32.1%, p=0.01 and p=0.03 by univariate and multivariate analysis, respectively). Integrin β1 was also found to be highly associated with the primary cancer site (oral cavity : larynx : oropharynx = 43.5% : 33.3% : 28.2%, p=0.01). Integrin β1 showed a proportional correlation with tumor stage (25.9% vs 45.9% for Stage III vs Stage IV, respectively, p = 0.02). In patients with metastasis, integrin β1 expression was inversely correlated with overall survival (p=0.02). The in vitro study showed that in integrin β1 knock-down cells, phosphorylation of FAK and MMP2 activity were down-regulated, which was associated with reduced invasion activity of these cells. Finally, the xenograft metastatic model showed that knock-down of integrin β1 significantly prevented HNSCC cells from metastasizing to the lymph node and lung (p=0.001 and p=0.02, respectively). Our study indicates that integrin β1 has a major impact on HNSCC prognosis through, at least partially, its active involvement in the regulation of metastasis. (Supported by NIH/NCI R21 CA125062 and GCC Distinguished Cancer Scholar award to ZGC and DMS)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2333.
Abstract 2339: Stimulation of sialyl Lewis X carbohydrate expression in lung carcinoma cells by neutrophils: Implications for metastasis
Authors: St. Hill Catherine A. , Farooqui Mariya , Krieser Katherine 
Published: February 2011

Abstract
Sialyl Lewis X (sLeX) is a carbohydrate epitope expressed on leukocytes and carcinoma cells that promotes binding of both cell types to vascular endothelium by selectin mediated processes. These binding events are crucial for leukocyte trafficking to lymphoid tissues and sites of inflammation and metastasis of cancer cells. Increased sLeX expression is correlated with advanced disease and a poor prognosis for several types of carcinomas. Synthesis of sLeX is dependent on activity of the enzymes α-(1,3)-fucosyltransferase (FucT-III) and α2,3-sialyltransferase. Exposure to tumor necrosis factor alpha (TNF-α) has been described to upregulate FucT-III resulting in increased sLeX in the airways of patients with respiratory disease, however, little is known about the molecular mechanisms involved in regulation of sLeX expression in the inflammatory tumor microenvironment. We stably transfected lung carcinoma cells with FucT-III to investigate the role of TNF-α in regulation of sLeX expression, selectin binding ability, and metastatic potential of lung carcinoma cells. Stimulation of FucT-III transfected but not mock-transfected H1299 and A549 lung carcinoma cells with recombinant TNF-α resulted in a concentration dependent upregulation of sLeX expression, increased binding of carcinoma cells to E-selectin, and increased migration of transfectants through Matrigel. Lung carcinoma cells transfected with FucT-III demonstrated high secretion of the neutrophil chemoattractant cytokines IL-8, GRO-α and MCP-1. Co-culture of lung carcinoma cells with neutrophil conditioned media and neutrophils isolated from blood at an optimal ratio of 1:5 resulted in significantly increased sLeX expression (p = 0.02 and p = 0.002 respectively). Exposure of transfected carcinoma cells to neutrophil conditioned media and neutrophils resulted in morphological changes consistent with increased invasive potential and a TNF-α dependent increased cellular migration through Matrigel. In patient lung carcinoma specimens but not in normal lung tissues, we observed areas of high sLeX expression that correlated with increased neutrophil infiltration in 80% of tumors. We conclude that FucT-III activity and sLeX expression in lung carcinomas may recruit neutrophils in the tumor microenvironment that enhance the metastatic potential of lung tumor cells. This work was supported in part by funds from the National Institutes of Health/National Cancer Institute grant K08 CA111829-04.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2339.
Abstract 2341: The Subtilisin-like proprotein convertases blockade inhibits the invasiveness of human primary melanoma with altered P53, CDKN2A and N-Ras genes
Authors: Lalou Claude , Scamuffa Nathalie , Podgorniak Marie-Pierre , Plassa Francois , Mourah Samia , Soufir Nadem , Dumaz Nicolas , Calvo Fabien , Basset-Seguin Nicole , KHATIB Abdel-Majid 
Published: February 2011

Abstract
Altered tumor suppressor p53 and/or CDKN2A as well as the Ras genes are frequently found in primary and metastatic melanomas. These alterations are responsible for the invasive/metastatic potential acquisition through their defective regulatory control on various MMPs and urokinase genes. Using primary human melanoma M10 cells with altered P53, CDKN2A and N-Ras genes, we found that inhibition of the proprotein convertases (PCs), enzymes involved in the proteolytic activation and/or expression of various cancer-related protein precursors reduced significantly their invasiveness. Analysis of M10 cells and their gastric and ganglion derived metastatic lesions revealed the presence of all the PCs found in the secretory pathway namely Furin, PACE4, PC5 and PC7. Expression of the general PCs inhibitor α1-PDX in these cells in a stable manner (M10/PDX) had no effect on the mRNA expression levels of these PCs. In vitro digestion assays and cell transfection experiments, revealed that M10/PDX cells present reduced PCs activity and are unable to process the PCs substrates proIGF-1R and proPDGF-A. These cells showed reduced migration, and invasion of Matrigel in vitro that paralleled decreased gelatinase MMP-2 activity and increased mRNA expression of tissue inhibitor of metalloproteinase 1 (TIMP-1) and TIMP-2. Furthermore, these cells showed decreased mRNA levels of urokinase-type plasminogen activator receptor (uPAR) and increased mRNA levels of plasminogen activator inhibitor-1 (PAI-1). Taken together, these data suggest that PCs activity inhibition has the ability to interfere with primary human melanoma cells invasiveness despite their altered P53, CDKN2A and N-Ras genes, suggesting the potential use of PCs as new therapeutic targets in melanoma.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2341.
Abstract 2346: Contribution of VLA-4 to ovarian cancer metastasis and platinum resistance
Authors: Scalici Jennifer M. , Harrer Christine , McLachlan Karen , Slack-Davis Jill 
Published: February 2011

Abstract
Ovarian cancer is the fourth leading cause of cancer-related death among women. The relatively poor prognosis for ovarian cancer (5-year survival of 30-40%) reflects 1) the advanced stage of disease at diagnosis and 2) the frequent development of recurrent disease refractory to front line therapy. Ovarian cancers metastasize by attaching to and invading through the mesothelium, a single cell layer of mesothelial cells lining the peritoneal cavity. The presence of invasive peritoneal metastases is associated with a poor prognosis for ovarian cancer (5 yr survival &lt;25%). We identified the integrin VLA-4 and its ligand VCAM-1 as regulators of mesothelial invasion. VLA-4 expression correlates with the ability of ovarian cancer cells to invade mesothelial monolayers. Additionally, VLA-4 is expressed on primary ovarian cancer cells obtained from patient tumors or ascites. The contribution of VLA-4 to ovarian cancer peritoneal metastasis was evaluated using a mouse xenograft model and function-blocking antibodies directed against VLA-4. Mice were injected intraperitoneally with platinum-resistant human ovarian cancer cells; one week later the mice were randomized into four groups and treated with 1) anti-VLA-4 antibodies, 2) carboplatin, 3) anti-VLA-4 and carboplatin, or 4) control IgG. Treatment with either anti-VLA-4 therapy or carboplatin alone had no effect on tumor burden compared to the IgG control group. However, the combined treatment of anti-VLA-4 and carboplatin significantly reduced tumor burden compared to the control or either treatment alone. This study supports a role for the active involvement of VLA-4 expressed by tumor cells in the regulation of ovarian cancer chemoresponsiveness.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2346.
Abstract 2348: Frzb/sFRP3 inhibits lung metastasis of osteosarcoma
Authors: Guo Yi , Christ Alexander , Czerwinski Ariel , Ni Rui , Xie Jun , Zi Xiaolin , Hoang Bang H 
Published: February 2011

Abstract
Osteosarcoma (OS) is the most common primary malignancy of bone. In spite of the recent advances in chemotherapy and surgery, 40-50% of the adolescent patients develop lung metastasis, 80% of patients with metastasis at diagnosis will relapse. Survival rate has shown no significant change over past 20 years. The molecular mechanism of metastasis of OS needs to be further explored and the novel anti-metastatic target needs to be developed. Our previous data showed that Frzb (also known as sFRP3), a secreted Fz-related protein, suppressed metastasis of fibrosarcoma. In this study, we examined the anti-metastatic effects of Frzb on OS, using the 143B and LM7 cell lines as a model. Frzb expression construct was stably transfected into 143B cells and LM7 cells. Over-expression of Frzb in OS cells was confirmed by real time PCR and western-blot. In a lung metastasis nude mice model, osteosarcoma LM7 cells expressing Frzb formed much fewer and much smaller lung metastatic nodules than control cells. Frzb also decreased in vitro cellular motility in a scratch wound assay. In order to determine the potential molecular mechanism underlying the anti-metastatic effect of Frzb on osteosarcoma, we examined the expression of c-Met, S100A4 and reversal of EMT (Epithelial Mesenchymal Transition). By real time PCR and western-blot assay, c-Met and S100A4, which were extensively reported to be involved in metastasis of different cancers, were both down-regulated by Frzb. However, most of epithelial markers (E-cadherin, keratin 8, keratin18, etc) and mesenchymal markers (N-cadherin, Vimentin, fibronectin) remained unchanged. Our study suggests that Frzb has strong anti-metastatic effect on osteosarcoma. The potential molecular mechanism may be through down-regulation of c-Met and S100A4 in OS cells by Frzb, instead of reversing the EMT. Therefore, strategies to over-express or deliver Frzb in osteosarcoma may lead to a reduction of lung metastasis
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2348.
Abstract 2349: DLC1 interaction with S100A10 mediates inhibition of in vitro cell invasion and tumorigenicity of lung cancer cells
Authors: Yang Xu-Yu , Popescu Nicolae C. , Zimonjic Drazen B. 
Published: February 2011

Abstract
Deleted in liver cancer 1 (DLC1) is a multidomain Rho-GTPase-activating protein (RhoGAP) and a tumor suppressor in several human common cancers. DLC1's structure predicts its interaction with a number of other proteins with various cellular functions. Previously we have shown that S100A10 (also known as p11), a key plasminogen receptor on the surface of cell membrane, colocalizes and binds with DLC1 in cell cytoplasm. The binding sites were mapped to the central domain of the DLC1 and at the end of C-terminus of S100A10. The same terminus is also a binding site for Annexin A2, which is believed to regulate availability of extracellular S100A10 and, therefore, dynamics of plasmin formation. Now we demonstrate that DLC1 competes with Annexin A2 for interaction with S100A10. DLC1 binding to S100A10 did not affect DLC1's RhoGAP activity but did reduce availability of S100A10 for binding by Annexin A2. Furthermore, the expression of DLC1 also affected S100A10 expression in a dose dependent manner, and increased S100A10 ubiquitin-dependent degradation. All of the above interactions attenuated plasminogen activation and resulted in inhibition of in vitro cell migration, invasion, colony formation and anchorage independent growth of aggressive and tumorigenic lung tumor cells. Transduction of DLC1-negative breast tumor cells significantly reduced the ability of tumor cells to form pulmonary metastases as well as inhibited distant dissemination of liver tumor cells in athymic mice. Current observations provide a plausible mechanism for DLC1 antimetastatic function by negatively affecting plasminogen activation, which in turn lead to a significant reduction in invasiveness of tumor cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2349.