bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A71: CD146 is a novel target of CD44-signaling mediating breast tumor invasion
Authors: Ouhtit Allal , Abdraboh Mohamed , Hollenbach Andrew D. , Gupta Ishita , Shanmuganathan Somya , Riyami Hamad Al , Errami Youssef , Farsi Yahya Al , Raj Madhwa HG 
Published: August 2014

Abstract
Cancer cell metastasis is one of the most critical steps in tumor development and is responsible for more than 80% of cancer related deaths. The cell adhesion molecule CD44 promotes cancer cell motility and metastasis. Despite this knowledge, the molecular mechanism through which CD44 promotes tumor development and cell metastasis is still unclear. The CD146 (MUC 18), another member of the cell adhesion molecules family, first identified in highly metastatic melanomas. The absence of CD146 in normal melanocytes and its high expression in melanomas suggests its tumor promoting actions. However, CD146 appears to suppress breast tumor progression. Furthermore, despite the association between CD146 expression and development of melanoma, the expression patterns and the role of CD146 in normal and metastatic breast tissues are still controversial. In a pilot study, we have identified CD146 as a potential downstream target of CD44-signaling in the MDA-435 breast cancer cell line, using subtractive hybridization and northern blot analyses. In this paper we provide evidence that CD146 is a downstream target for CD44, in a way that CD146 expression is regulated according to tumor microenvironment. Finally, this study demonstrates a new role for CD44 in regulating neovascularization and promoting cancer cell transmigration of blood vessels via CD146.
Citation Format: Allal Ouhtit, Mohamed Abdraboh, Andrew D. Hollenbach, Ishita Gupta, Somya Shanmuganathan, Hamad Al Riyami, Youssef Errami, Yahya Al Farsi, Madhwa HG Raj. CD146 is a novel target of CD44-signaling mediating breast tumor invasion. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr A71.
Abstract A72: TGF-β2 underpins CD44-promoted breast tumor cell invasion
Authors: Ouhtit Allal , Madani Samineh , Gupta Ishita , Shanmuganathan Somya , Al-Riyami Hamad , Al-Farsi Yahya 
Published: August 2014

Abstract
Hyaluronan (HA) mediates communication between cancer cells and the environment via interactions with the cell surface receptor CD44. The long-term objective of this study is to increase our understanding of the mechanisms by which CD44-HA interaction promotes BC metastasis, and further identify and validate CD44-downstream transcriptional targets for anti-metastatic therapy. Here, we have developed a tetracycline (tet)-regulated expression of CD44 gene in the BC cell line MCF-7 (B5 clone) and identified TGF-beta2 (Transforming Growth Factor beta-2; 3 fold induction) as a potential CD44s-downstream transcriptional target by microarray analysis. The same RNA samples, used for microarray analysis and their corresponding protein lysates, were examined for CD44 expression by RT-PCR and western-Blot methods, respectively. TGF-beta2 mRNA levels were significantly elevated following the removal of tet at 18, 24, and 48 h post-HA stimulation compared to controls. Furthermore, the TGF-beta2 precursor protein increased in a time-dependent pattern upon HA-stimulation and in the absence of tet. Inhibition of CD44 gene by RNAi method decreased TGF-beta2 expression upon HA-stimulation and in the absence of tet. Our data put together strongly support the hypothesis that TGF-beta2 is a potential target of HA/CD44-downstream-signaling mediating BC cell invasion. Finally, CREB might be the transcription factor linking CD44 to TGF-beta2 transcription.
Citation Format: Allal Ouhtit, Samineh Madani, Ishita Gupta, Somya Shanmuganathan, Hamad Al-Riyami, Yahya Al-Farsi. TGF-β2 underpins CD44-promoted breast tumor cell invasion. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr A72.
Abstract A82: The role of PI3-kinase signaling pathway in invadopodia formation
Authors: Yamaguchi Hideki , Yoshida Nachi , Sakai Ryuichi 
Published: August 2014

Abstract
Degradation of extracellular matrix that is present in the basement membrane and tumor stroma is essential for local invasion and formation of metastatic sites by malignant cancer cells. Invadopodia are extracellular matrix-degrading protrusions formed by invasive cancer cells that have been shown to function in cancer invasion and metastasis. Although many invadopodia components have been identified, signaling pathways that link extracellular stimuli to invadopodia formation remain poorly understood. The phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that phosphorylate phosphoinositides at the D-3 position of the inositol headgroup. PI3Ks mediate the signal transduction of extracellular stimuli and regulate diverse cellular events. Uncontrolled activation of the PI3K signaling pathway leads to tumorigenesis and tumor malignancy. In this study, we investigated the role of PI3K signaling during invadopodia formation. We found that in human breast cancer cells both invadopodia formation and degradation of a gelatin matrix were blocked by treatment with PI3K inhibitors or sequestration of D-3 phosphoinositides. Functional analyses revealed that among the PI3K family proteins the class I PI3K catalytic subunit p110α, a frequently mutated gene product in human cancers, was selectively involved in invadopodia formation. The expression of p110α with cancerous mutations promoted invadopodia-mediated invasive activity. Furthermore, knockdown or inhibition of PDK1 and Akt suppressed invadopodia formation induced by p110α mutants. These data suggest that PI3K signaling via p110α regulates invadopodia-mediated invasion of breast cancer cells.
Citation Format: Hideki Yamaguchi, Nachi Yoshida, Ryuichi Sakai. The role of PI3-kinase signaling pathway in invadopodia formation. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr A82.
Abstract A89: Sulfated polysaccharides from marine brown alga alleviate pancreatic cancer metastasis
Authors: Delma Caroline R. , Thirugnanasambandan Somasundaram S. , Srinivasan Guruprasad , Aravindan Sheeja , Natarajan Mohan , Herman Terence S. , Aravindan Natarajan 
Published: August 2014

Abstract
Pancreatic cancer is one of the most deadly cancers with a five year survival rate of less than six percent. The poor prognosis can be attributed to the fact that more than three fourth of the patients have metastasis at the time of diagnosis. In view of the increasing evidence that sulfated polysaccharides attenuate tumor invasion, we attempted to evaluate the anti-metastatic potential of sulfated polysaccharide fractions from a marine brown alga, Turbinaria conoides in pancreatic cancer. Exposure of human pancreatic adenocarcinoma cells (MiaPaCa-2, Panc-1, BxPC-3 and Panc-3.27) to partially purified polysaccharide fractions showed a negative regulation of both the transcriptional activation (QPCR) and cellular expression (immunoblotting) of adhesion molecules, Mucin-16, E-Selectin and metastasis efficiency modifying SPA 1 and Dnmt3b. All encompassed, transcriptional profiling pertaining to tumor invasion and metastasis (QPCR profiling) revealed cell-type unique, yet comprehensive inhibition, including 62, 65, 64 and 51 of 93 transcripts in Mia PaCa-2, Panc-1, BxPC3 and Panc-3.27 cells, respectively. Extracellular matrix metalloproteinases MMP-2 and MMP-9, which play a significant and definite role in the invasion and metastasis of pancreatic cancer were completely muted as evidenced by reduced activity (by gelatin zymography) and secretion (by immunoblotting) in cells exposed to all fractions. Relatively, fraction V showed robust inhibitory potential in this setting. Together, these data suggest that fractions of sulfated polysaccharides, specifically fraction V, may serve as a potential drug deliverable to alleviate pancreatic cancer metastasis. This study prompts us to investigate further the active constituents in the sulfated polysaccharide fraction and their target binding affinity, (here in this case, to MUC16 and/or MMPs) and their mode of signal transduction. These in vitro studies and studies testing its efficacy in an in vivo setting are currently in process in our laboratory.
Citation Format: Caroline R. Delma, Somasundaram S. Thirugnanasambandan, Guruprasad Srinivasan, Sheeja Aravindan, Mohan Natarajan, Terence S. Herman, Natarajan Aravindan. Sulfated polysaccharides from marine brown alga alleviate pancreatic cancer metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr A89.
Abstract B100: Genomic copy number alterations associated with the early brain metastasis of non-small cell lung cancer
Authors: Lee Hye Won , Lee Se Jeong , Song Mi Young , Joo Kyeung Min , Nam Do-Hyun 
Published: August 2014

Abstract
Frequent early development of systemic metastasis leads unfavourable clinical prognosis of the non-small cell lung cancer (NSCLC). Although the brain metastasis (BM) contributes significantly to the morbidity and mortality of NSCLC, relevant driver mechanisms are largely unknown. To elucidate genetic alterations and prognostic markers associated with early BM of NSCLC, we retrospectively collected 18 NSCLC patients with BM (12 adenocarcinomas (ADC) and 6 squamous cell carcinomas (SQCC)) whose surgical tissues of primary and/or metastatic tumors were preserved as formaldehyde fixed and paraffin embedded (FFPE) pathologic samples. When chromosomal copy number alterations (CNAs) of those FFPE samples were analysed by the Molecular Inversion Probe (MIP) technology, the most frequent CNAs detected in primary ADCs were gains of 3q, 5p, 5q, 6p, 8q, 9p, 11p, 15q, 17q and losses of 10q and 22q whereas primary SQCCs revealed gains in 4q and 12q and loss in 9q. Moreover, comparative MIP analysis on 11 matched cases demonstrated the fact that the BM carried the majority of genetic alterations present in the corresponding primary tumor but with a slightly higher frequency including gain of 9p11 and loss of 2p11 in ADCs. Especially, when primary 12 ADCs were analyzed depending on the pattern of BM to uncover predetermining signatures that can predict the risk of BM, selectively amplified regions of primary lung ADCs (5q35, 10q23 and 17q23-24) were identified as significantly associated with the development of early BM within 3 months after first diagnosis of primary tumor. Small interfering RNA silencing of ACTA2, which is one of several candidate genes revealed in this study, reduced the in vitro migratory and invasive potential of human ADC cell line PC14PE6-GFP tagged cells without affecting on proliferation. Although more validation is needed, the genetic signatures elucidated in this study shed light on the molecular mechanisms involved in BM and help to identify prognostic markers stratifying the subgroup at high risk of developing recurrence or distant metastasis within heterogeneous NSCLC patients.
Citation Format: Hye Won Lee, Se Jeong Lee, Mi Young Song, Kyeung Min Joo, Do-Hyun Nam. Genomic copy number alterations associated with the early brain metastasis of non-small cell lung cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B100.
Abstract B18: MiR-205 puts the brakes on the malignant interplay between prostate cancer cells and associated fibroblasts
Authors: Gandellini Paolo , Giannoni Elisa , Casamichele Anna , Taddei Maria Letizia , Callari Maurizio , Valdagni Riccardo , Zaffaroni Nadia , Chiarugi Paola 
Published: August 2014

Abstract
Tumor microenvironment is a strong determinant for the acquisition of metastatic potential of cancer cells. We have recently demonstrated that cancer associated fibroblasts (CAFs) elicit an epithelial-mesenchymal transition (EMT) in prostate cancer (PCa) cells, leading to enhanced tumor cell aggressiveness. Here, we investigated the involvement of microRNAs (miRNA) in such malignant tumor-stroma interplay, to identify possible tools to prevent metastasis dissemination. We found that miR-205 is the most down-modulated miRNA in PCa cells upon CAF stimulation and acknowledged HIF-1 to be a direct repressor of miRNA transcription. Rescue experiments demonstrated that ectopic miR-205 over-expression in PCa cells counteracts CAF-induced EMT, thus impairing enhancement of cell invasion, acquisition of stem cell traits, tumorigenicity and metastatic dissemination. In addition, miR-205 can block tumor-driven activation of surrounding fibroblasts, by reducing pro-inflammatory cytokine secretion. Overall, these findings suggest a key role of miR-205 in the bidirectional interplay between PCa cells and fibroblasts. In addition, the evidence that miR-205 replacement in PCa cells is able not only to prevent but also to revert EMT induced by CAFs sets up the rationale for developing miRNA-based approaches for the prevention and treatment of aggressive tumors.
Citation Format: Paolo Gandellini, Elisa Giannoni, Anna Casamichele, Maria Letizia Taddei, Maurizio Callari, Riccardo Valdagni, Nadia Zaffaroni, Paola Chiarugi. MiR-205 puts the brakes on the malignant interplay between prostate cancer cells and associated fibroblasts. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B18.
Abstract B31: An interspecies comparison between the structure and products of the parathyroid hormone-related peptide gene
Authors: Freeman Adam , Martin T. J. 
Published: August 2014

Abstract
The Parathyroid Hormone-related Peptide (PTHrP) is widely expressed across many species. It acts as a key regulator of cellular metabolic control, including calcium metabolism, and plays a significant role in the development and maintenance of many normal tissues. It also plays an intriguing role in neoplasia of multiple organs, and is thought integral to Breast Cancer in particular. PTHrP has been characterised in many animals in addition to humans. A review of the contemporaneous literature was performed to make this comparison. Although its complexity and composition differ, the PTHrP gene has been shown to have several well-conserved regions across different species; gene products have demonstrated physiological inter-species activity. Three main functional domains have been identified in humans, with similarities in other species. Examination of these areas has yielded insight into the physiology and function of the gene. In humans, potential splicing of PTHrP pre-messenger RNA yields three potential isotypes of 139, 141, and 173 amino acids. Whereas rats and mice produce 141 and 139; chickens several 139 amino acid peptides; Xenopus a 144 and 131; sea bream125 and 126 ; and the elephant shark a single 156 amino acid product. These genes are represented graphically and a review of functional domains is performed.
Citation Format: Adam Freeman, T. J. Martin. An interspecies comparison between the structure and products of the parathyroid hormone-related peptide gene. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B31.
Abstract B42: Dichotomus role of profilin in early vs. late steps of breast cancer metastasis
Authors: Roy Partha 
Published: August 2014

Abstract
Profilin1 (Pfn1), an essential control element for actin polymerization, plays indispensable role in migration and proliferation of normal cells. Seemingly contrary to these essential cellular functions of Pfn1, its expression is downregulated in breast cancer, the significance of which is unclear. In this study, expression profiling of Pfn1 in human breast cancer specimens of various histopathological stages correlate lower Pfn1 expression levels with propensity to metastasize. Xenograft studies uncover a unique dichotomous role of Pfn1 in early vs late steps of breast cancer metastasis. Specifically, loss of Pfn1 expression promotes dissemination of breast cancer cells from the primary mammary tumor but metastatic colonization of breast cancer cells is critically dependent on Pfn1's function. In the context of dissemination, breast cancer cells exhibit increased sustenance of PI3K signaling and acquire a hyper-invasive phenotype (marked by MMP9 upregulation, faster invasion through collagen matrix) involving a PI3K-PI(3,4)P2 signaling axis when Pfn1 expression is suppressed. In addition, Pfn1-deficient breast cancer cells display increased proficiency to cross through an endothelial cell barrier (an obligatory step for vascular dissemination) in a VEGF-dependent manner, respectively. Gene expression profiling combined with biochemical analyses of secreted proteins show that loss of Pfn1 impacts expression of several other pro-invasive and pro-metastatic genes. Finally, correlated with hyper-invasive phenotype of breast cancer cells caused by Pfn1 depletion, we found that mammary-specific deletion of Pfn1 gene expedites ductal outgrowth. In summary, contrasting the well-established pro-migratory role of Pfn1 in the physiological contexts, our findings set the first in vivo example of a context-specific effect of loss of Pfn1 in cell motility-dependent processes such as mammary gland morphogenesis and metastatic dissemination.
Citation Format: Partha Roy. Dichotomus role of profilin in early vs. late steps of breast cancer metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B42.
Abstract B47: New role for α-catenin family member α-catulin in squamous cell carcinoma invasion and metastasis.
Authors: Cao Christine , Chen Yibu , Masood Rizwan , Sinha Uttam , Kobielak Agnieszka 
Published: August 2014

Abstract
The capacity of tumor cells to produce metastases is the main features of malignant tumors and the main causes of death for cancer. Squamous cell cancers comprise the most common types of human epithelial cancers. One subtype, head and neck squamous cell carcinoma (HNSCC), is a particularly aggressive cancer with poor prognosis due to late diagnosis and metastasis. Here we find that in vivo, the α-catenin homologue — α-catulin, is highly expressed at the tumor invasion front and in the metastatic streams of cells in both malignant human HNSCCs and a mouse model of oral SCC. Knockdown of α-catulin in hHNSCC cell lines dramatically decrease the migratory and invasive potential of those cells in vitro and metastatic potential in xenotransplants in vivo. Analysis of tumors deficient in α-catulin showed that the tumor cells are unable to invade the surrounding stroma. Accordingly, transcriptional profiling of those tumors revealed that α-catulin ablation is accompanied by changes in genes involved in cell migration and invasion. In vitro an upregulation of α-catulin expression correlates with the transition of tumor cells from an epithelial to a mesenchymal morphology, as well as an upregulation of EMT markers vimentin and snail. Overall, these results strongly indicate that α-catulin contributes to the invasive behavior of metastatic cells, and may be used as a prognostic marker and future therapeutic target for cancer patients.
Citation Format: Christine Cao, Yibu Chen, Rizwan Masood, Uttam Sinha, Agnieszka Kobielak. New role for α-catenin family member α-catulin in squamous cell carcinoma invasion and metastasis.. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B47.
Abstract B56: A lineage-selective transcriptional pathway linking lung differentiation and cancer metastasis
Authors: Cheung William K.C. , Zhao Minghui , Liu Zongzhi , Cao Paul D. , Stevens Laura E. , Westbrook Thomas F. , Nguyen Don X. 
Published: August 2014

Abstract
Lung cancer is the leading cause of cancer-related deaths worldwide. This poor prognosis is due to the rapid metastatic progression of this disease, yet the mechanisms that govern lung cancer dissemination and colonization are unclear. Through an integrated approach, we identified an alveolar cell-selective gene signature that stratifies lung adenocarcinoma (ADC) into molecular subtypes of distinct prognosis and differentiation states. This transcriptional program is regulated in part by the cell fate transcription factors, GATA6 and HOPX, which are normally required for proper alveolar differentiation. In an experimental model, suppression of GATA6 and HOPX cooperatively enhances metastatic competence of lung ADC cells. Whole genome RNA sequencing reveals that this transcriptional network can modulate specific target genes and pathways involved in airway epithelial differentiation and invasion. Our findings identify a novel cell lineage molecular program whose perturbation enhances lung cancer metastasis.
Citation Format: William K.C. Cheung, Minghui Zhao, Zongzhi Liu, Paul D. Cao, Laura E. Stevens, Thomas F. Westbrook, Don X. Nguyen. A lineage-selective transcriptional pathway linking lung differentiation and cancer metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B56.