bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5179: An endothelial-mesenchymal transition of brain endothelial cells is required for metastatic extravasation
Authors: Krizbai Istvan A. , Gasparics Akos , Nagyoszi Peter , Fazakas Csilla , Wilhelm Imola , Bencs Rita , Rosivall Laszlo , Sebe Attila 
Published: August 2015

Abstract
Endothelial-mesenchymal transition (EndMT) is an embryonic program necessary for organ development. Despite being normally dormant in adult organisms, this mechanism can be reactivated during several pathological conditions, such as cancer and fibrosis. EndMT is characterized by the downregulation of the endothelial program, activation of the mesenchymal-fibrogenic program, and finally the activation of the myogenic program. Cancer progression towards metastasis follows a defined sequence of events described as the metastatic cascade. For extravasation and transendothelial migration metastatic cells interact first with endothelial cells. Yet the role of endothelial cells during the process of metastasis formation and extravasation is still unclear, and the interaction between metastatic and endothelial cells during transendothelial migration is poorly understood. Since tumor cells are well known to express TGF-β, and the compact endothelial layer undergoes a series of changes during metastatic extravasation (cell contact disruption, cytoskeletal reorganization, contractility), we hypothesized that an EndMT may be necessary for metastatic extravasation.
We show that primary rat brain endothelial cells (BECs) undergo EndMT upon TGF-β1 treatment, characterized by the loss of tight and adherent junction proteins, the expression of fibronectin, β1-integrin, calponin and α-smooth muscle actin (SMA), and an increase in N-cadherin levels. B16/F10 activated conditioned medium (ACM) induced claudin-5 downregulation, fibronectin and SMA expression in BECs. Inhibition of TGF-β signaling during B16/F10 ACM stimulation using SB-431542 maintained claudin-5 levels and mitigated fibronectin and SMA expression. SB-431542 prevented SMA upregulation upon stimulation of BECs with A2058, MCF-7 and MDA-MB231 ACM. Moreover, B16/F10 ACM caused a reduction in transdendothelial electrical resistance and enhanced the number of melanoma cells adhering to the endothelial layer, both in a TGF- β dependent manner. Finally, pretreatment with TGF-β1 or B16/F10 ACM enhanced transendothelial migration of B16/F10 cells.
Our results indicate that an EndMT may be necessary for metastatic transendothelial migration, and may play a relevant role during the complex phenomenon known as metastatic extravasation.
Citation Format: Istvan A. Krizbai, Akos Gasparics, Peter Nagyoszi, Csilla Fazakas, Imola Wilhelm, Rita Bencs, Laszlo Rosivall, Attila Sebe. An endothelial-mesenchymal transition of brain endothelial cells is required for metastatic extravasation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5179. doi:10.1158/1538-7445.AM2015-5179
Abstract 5183: Identification and characterization of wild type kinases driving prostate cancer metastasis
Authors: Faltermeier Claire , Drake Justin , Clark Peter , Smith Bryan , Mathis Colleen , Zong Yang , Volpe Carmen , Witte Owen 
Published: August 2015

Abstract
Despite numerous oncogenic alterations implicated in metastatic prostate cancer, mutations or DNA amplifications of kinases are rare. We previously demonstrated that 1) expression of wild type (wt) Src in combination with the androgen receptor synergizes to produce aggressive prostate adenocarcinoma, 2) tyrosine phosphorylation increases with prostate cancer stage, and 3) the phosphoproteomic profile of metastatic prostate cancer is different from localized disease. However, the question still remains as to whether wt kinases can drive prostate cancer metastasis and should be regarded as therapeutic targets. To identify wt kinases driving prostate cancer metastasis, we performed phospho-tyrosine, threonine and serine peptide enrichment and quantitative mass spectrometry on metastatic prostate cancer tissues obtained at rapid autopsy. Analysis of this phosphoproteomic dataset combined with bioinformatic analyses of genomic datasets identified ∼140 kinases differentially expressed or activated in prostate cancer metastases. To determine which of these kinases function to promote prostate cancer metastasis, we developed an in vitro and in vivo metastasis screen. Out of 140 kinases, 20 kinases promote resistance to anoikis in vitro and metastatic colonization in vivo. Positive kinases include Src, Lyn, and EGFR which have been previously reported to be important in prostate cancer metastasis and thus provide strength to the validity of our screen. In addition we identified kinases with uncharacterized roles in prostate cancer metastasis and of particular interest, several of these kinases promote bone metastasis. We expect our findings will improve our understanding of the mechanistic role of kinase activation in prostate cancer and identify promising new therapeutic targets for metastatic disease.
Citation Format: Claire Faltermeier, Justin Drake, Peter Clark, Bryan Smith, Colleen Mathis, Yang Zong, Carmen Volpe, Owen Witte. Identification and characterization of wild type kinases driving prostate cancer metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5183. doi:10.1158/1538-7445.AM2015-5183
Abstract 5189: Inhibitory effect of phytochemicals on oncostatin-M-induced tumor invasion and migration in human esophageal carcinoma
Authors: Naka Eijin , Takahashi Yuko , Matsubara Hisahiro , Kato Kazunori 
Published: August 2015

Abstract
An epithelial-to-mesenchymal transition (EMT) is one of important phenomenon in tumor metastasis. Oncostatin-M (OSM) belonging to the IL-6 family is a cytokine that participates in invasion and migration of various cancer cells. It is produced by macrophage and stimulates the JAK/STAT signal transduction pathway. In this study, we examined the effect of OSM on EMT of human esophageal carcinoma cells and found a way to inhibit cell metastasis. We first observed morphological changes of tumor cells from an epithelial-like phenotype to a more spindle-shaped, mesenchymal phenotype by OSM. Consistent with these findings, OSM also promoted cell motility using a wound scratch assay and matrigel invasion assay. Moreover, we observed that intracellular stat3 phosphorylation was promoted by the stimulation of OSM by Western blotting. To confirm the contribution of p-stat3, we used a selective JAK2/STAT3 inhibitor cucurbitacin I. As a result, cucurbitacin I strongly inhibited OSM-induced tumor cell invasion and migration. Then, we used two dietary phytochemical resveratrol (polyphenol in grapes) and sulforaphane (isothiocyanate in broccolis), both were reported as candidates of stat3 inhibitor. By the addition of resveratrol or sulforaphane, we found that these markedly inhibited OSM-induced stat3 phosphorylation, the expression of EMT-related genes (snail, slug and vimentin) and tumor cell migration. Overall, our findings provide new evidence that these phytochemicals suppress OSM-induced tumor invasion and migration through inhibiting stat3 phosphorylation and EMT pathway.
Citation Format: Eijin Naka, Yuko Takahashi, Hisahiro Matsubara, Kazunori Kato. Inhibitory effect of phytochemicals on oncostatin-M-induced tumor invasion and migration in human esophageal carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5189. doi:10.1158/1538-7445.AM2015-5189
Abstract 5190: CCR6-mediated molecular mechanisms involved in colon cancer
Authors: Kapur Neeraj , Mir Hina , Singh Rajesh , Singh Shailesh 
Published: August 2015

Abstract
Colon cancer is one of the leading causes of death due to cancer worldwide. Molecular mechanism of initiation and progression of this disease is yet to be defined. Chemokines and their corresponding receptors have been shown to play important role in progression of many cancers including colon. In this study we have demonstrated that CCR6 is highly expressed in colon cancer and is associated with key steps of metastasis. Cell migration, adhesion and invasion are the key features of cancer progression. This process initiates with the change of less motile epithelial phenotype to a more motile mesenchymal type, the phenomenon known as epithelial-mesenchymal transition (EMT). Interestingly, stimulation of colon cancer cell with CCL20, which is the only natural ligand for CCR6, showed significant decrease in E-cadherin. Furthermore, increased Vimentin, beta-Catenin, N-cadherin, alpha-Smooth Muscle Actin (αSMA) and Snail following CCL20 treatment implicates potential role of CCR6-CCL20 axis in transition to mesenchymal phenotype. Hence, strategies directed to this chemokine-receptor axis may improve therapeutic outcome of colon cancer.
Citation Format: Neeraj Kapur, Hina Mir, Rajesh Singh, Shailesh Singh. CCR6-mediated molecular mechanisms involved in colon cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5190. doi:10.1158/1538-7445.AM2015-5190
Abstract 5191: Missense mutants of p53 tumor suppressor contributes to drug-resistance and epithelial-mesenchymal transition in colon cancer cells
Authors: Hosain Salman B. , Liu Yong Y. 
Published: August 2015

Abstract
The mutants of p53 tumor suppressor that have been detected in approximately 50% of tumors exhibit oncogenic function and promote tumor progression. Restoration of tumor suppression by introduction of wild-type p53 effectively eliminate cancers in preclinical studies; however, more than 80% of p53 mutations are missense mutants, those can form heterotetramers and diminish the therapeutic effect of p53 transgene. It is still unclear how missense mutants promote tumor progression, particularly in whether or not these mutants contribute to induced cancer stem cells during chemotherapy. We report herewith that R273 missense mutant contributes to drug-induced stem cell-like behavior in colorectal cancer cells. Heterozygous SW48 TP53 (R273H/+) cells presented the same sensitivity to doxorubicin and paclitaxel as its parental SW48 colon cancer cells. However, after exposure to lower concentrations of doxorubicin (10 nM) or paclitaxel (4 nM) for eight weeks, SW48 TP53 not only were resistant to anticancer drugs, but also displayed an epithelial-mesenchymal transition (EMT). With the overexpressed E-cadherin and down-expressed vimentin, SW48 TP53 cells that were exposed to doxorubicin displayed significantly EMT morphological changes and increased wound healing, compared to SW 48 cells. Interestingly, inhibition of ceramide glycosylation with PDMP to increase endogenous ceramide restored wild-type p53 expression in heterozygous SW48 TP53 cells exposed to doxorubicin and further sensitized these cells to anticancer drugs and reversed EMT. These findings indicate that a heterozygous missense p53 mutant promotes EMT and drug resistance of colon cancer cells in chemotherapy, and restoration of p53 expression with suppression ceramide glycosylation can improve therapeutic efficacy.
Citation Format: Salman B. Hosain, Yong Y. Liu. Missense mutants of p53 tumor suppressor contributes to drug-resistance and epithelial-mesenchymal transition in colon cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5191. doi:10.1158/1538-7445.AM2015-5191
Abstract 5193: Ataxia telangiectasia mutated relates to epithelial-mesenchymal transition in colorectal cancer
Authors: Takahashi Hidena , Tsuruta Masashi , Hasegawa Hirotoshi , Okabayashi Koji , Seishima Ryo , Matsui Shimpei , Yamada Toru , Kondo Takayuki , Shimada Takehiro , Matsuda Mutsuhito , Yahagi Masashi , Yoshikawa Yusuke , Asada Yusuke , Sugiura Kiyoaki , Suzuki Yoshiyuki , Tajima Yuki , Nakadai Junpei , Kitagawa Yuko 
Published: August 2015

Abstract
Background: The Ataxia telangiectasia mutated (ATM) is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks. Recently, ATM was reported to correlate with breast cancer metastasis by regulating phosphorylated Snail which was known as a marker of epithelial-mesenchymal transition (EMT), however, it remains unclear in colorectal cancer (CRC). In this study we attempted to clarify the impact of ATM on the mechanism of EMT in CRC.
Methods: Potential ATM levels were evaluated in human CRC cells (HT29 and SW480) by qPCR and western blot analysis. Cells were induced EMT by treated with TGF-b, were confirmed by the change of EMT markers (i.e. N-cadherin, E-cadherin, Snail and twist). Next, ATM levels were down-regulated by siRNA and the impact on EMT were evaluated by EMT markers. Invasive potential was evaluated by scratch assay.
Results: HT29 showed significantly higher levels of ATM comparing to SW480 (p = 0.042). N-cadherin (p = 0.065), Snail (p = 0.034) and twist (p = 0.052) were highly observed in HT-29, while similar level of E-cadherin in SW480 (p = 0.692). Scratch assay revealed that approximately 4 times high migration was observed in HT29. TGF-b induced EMT such as elevation of N-cadherin and Snail (E-cadherin was not affected), leading to promotion of cell migration in SW480. ATM was successfully 48.4% down-regulated (p = 0.001) in SW480, which resulted in reducing cell migration (p = 0.033).
Conclusions: ATM might be a critical regulator of EMT in colorectal cancer invasion.
Citation Format: Hidena Takahashi, Masashi Tsuruta, Hirotoshi Hasegawa, Koji Okabayashi, Ryo Seishima, Shimpei Matsui, Toru Yamada, Takayuki Kondo, Takehiro Shimada, Mutsuhito Matsuda, Masashi Yahagi, Yusuke Yoshikawa, Yusuke Asada, Kiyoaki Sugiura, Yoshiyuki Suzuki, Yuki Tajima, Junpei Nakadai, Yuko Kitagawa. Ataxia telangiectasia mutated relates to epithelial-mesenchymal transition in colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5193. doi:10.1158/1538-7445.AM2015-5193
Abstract 5197: Claudin-1 enhances tumor proliferation and metastasis by regulating cell anoikisin gastric cancer
Authors: Li Jiangfang , Huang Jie , Liu Bingya , Zhu Zhenggang 
Published: August 2015

Abstract
Claudin-1 (CLDN1) is overexpressed in gastric cancer and correlated with tumor invasion, metastasis and poor outcome. Here, we both down and up regulated CLDN1 expression in gastric cancer cells to elucidate its role in gastric carcinogenesis and tumor progression. As results, we found that deficiency of CLDN1 inhibited cells migration, invasion, and colony formation in vitro and tumorigenicity, metastasis in vivo. Furthermore, CLDN1 expression promoted cell aggregation and increased anoikis resistance. Down or up regulated CLDN1 were accompanied with variations of membrane β-catenin expression and activities of Akt and Src signals. When β-catenin was up-regulated in CLDN1-KD cell, cell aggregation and anoikis resistance were restored, and Akt and Src signal pathways were re-activated. Taken together, these findings suggested that CLDN1 may function as an oncogene in gastric cancer and its malignant potential may attribute to the regulation of cell anoikis through mediating membrane β-catenin regulated cell-cell adhesion and survival signals of Akt and Src.
Note: This abstract was not presented at the meeting.
Citation Format: Jiangfang Li, Jie Huang, Bingya Liu, Zhenggang Zhu. Claudin-1 enhances tumor proliferation and metastasis by regulating cell anoikisin gastric cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5197. doi:10.1158/1538-7445.AM2015-5197
Abstract 520: MIEN1 drives breast cancer invasion by regulating cytoskeletal dynamics
Authors: Kpetemey Marilyne , Vishwanatha Jamboor 
Published: August 2015

Abstract
Introduction: The emergence of metastases remains the primary cause of cancer mortality and morbidity. Active migration of tumour cells is a prerequisite for tumor-cell invasion and metastasis. We identified Migration and Invasion Enhancer 1(MIEN1) as a novel promoter of cell migration/invasion.
Previously known as C35, C17orf37, RDX12 and MGC14832, MIEN1 is a novel gene located in the chromosomal region 17q12-21. While absent or low in normal tissues, MIEN1 is abundantly expressed in multiple cancers including breast carcinomas. A membrane-bound signaling adaptor, MIEN1 localizes to the leading edge of migrating cells and promotes migration and invasion by increasing filopodium formation. While MIEN1 is shown to promote motility through filopodia formation, little is known on the mechanisms by which MIEN1 influence the actin cytoskeleton. Exploring underlying mechanisms, we show that MIEN1 associates with the actin cytokeleton during motility and directly influence actin polymerization.
Methods: We performed immunofluorescence, migration and invasion assays using breast cancer cell lines, MDA-MB 231 and MCF10CA1a to investigate the mechanisms by which MIEN1 potentiates cell motility.
Results: Ablation of MIEN1 inhibited cell migration, cell adhesion and altered the phosphorylation status of motility markers. Immunofluorescence staining with FITC- conjugated-phalladoin confirmed that alteration of MIEN1 expression leads to reconfiguration of the actin cytoskeleton in breast cancer cells. Furthermore we found that MIEN1 associates with cytoskeletal proteins involved in motility processes.
Conclusion: Our results show that MIEN1 is a critical regulator of cell migration and invasion. The importance of MIEN1 in tumor cell dissemination is well established; understanding the molecular mechanisms aiding the processes involved will enable the design of novel and effective treatments for metastatic tumors.
Citation Format: Marilyne Kpetemey, Jamboor Vishwanatha. MIEN1 drives breast cancer invasion by regulating cytoskeletal dynamics. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 520. doi:10.1158/1538-7445.AM2015-520
Abstract 5201: Antimetastatic effect of a Dializable Leucocyte Extract in a murine model of prostate cancer
Authors: Hernandez-Esquivel Miguel A. , Perez-Tapia Sonia M. , Pestell Richard G. , Velasco-Velazquez Marco A. 
Published: August 2015

Abstract
Prostate cancer remains the most common non-dermatological cancer in the United States and the second leading cause of cancer death amongst men. The majority of men with progressive prostate cancer develop metastases, being the skeleton the most prevalent metastatic site. Dialyzable leukocyte extracts (DLEs) are heterogeneous mixtures of low-molecular-weight (&lt;10 kDa) peptides that improve clinical responses in various diseases. Our group has shown that DLEs change cytokine serum concentrations in patients and reduce experimental metastasis in a melanoma model. In this work we analyzed the in vitro effects of a human DLE produced under good manufacturing procedures and facilities [1] and evaluated its possible antimetastatic effect in vivo.
We employed PC-3 cells and murine Src-transformed Prostate Epithelial Cells (PEC-Src) to assess the direct effects of DLE in prostate cancer cells. Both cell lines were exposed in vitro to the DLE (1 pg/mL- 1 μg/mL) in proliferating (+FBS) or non-proliferating (-FBS) conditions, and cell number was estimated by MTS assays. The effects on cell motility and cell invasion were evaluated by wound healing assays and invasion from collagen-embedded spheroids, respectively. Since DLEs are immunomodulators, we used an experimental metastasis model that consistently produces bone and brain metastasis in inmunocompetent mice [2]. PEC-Src expressing Luciferase2-RFP were intracardiacally injected to FVB mice and metastatic growth in DLE-treated (1, 5, or 25 μg/kg p.o.) animals was quantified weekly by bioluminescence imaging.
In vitro exposure to a wide range of DLE concentrations did not alter proliferation or survival in PC-3 or PEC-Src cells, indicating that the evaluated DLE does not has direct antineoplastic effect. Similarly, treatments did not alter prostate cancer cell motility or invasion. In contrast, DLE (1 μg/kg) reduced metastatic tumor burden in brain and bones in inmunocompetent mice. The absence of direct effect on prostate cancer cells suggests that DLE-treatment may be changing cellular or soluble facilitators in the metastatic microenvironments. Supported by PAPIIT-UNAM IN219613.
[1] Medina-Rivero E, et al. J Pharma Biomed Anal 88: 289-294, 2014
[2] Sicoli D, et al. Cancer Res 74: 7103-14, 2014
Citation Format: Miguel A. Hernandez-Esquivel, Sonia M. Perez-Tapia, Richard G. Pestell, Marco A. Velasco-Velazquez. Antimetastatic effect of a Dializable Leucocyte Extract in a murine model of prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5201. doi:10.1158/1538-7445.AM2015-5201
Abstract 5209: Non-tumoral autotaxin stored into platelet α-granules promotes breast cancer cell metastasis
Authors: Leblanc Raphael , Lee Sue-Chin , Norman Dereck , Ribeiro Johnny , Tigyi Gabor , Peyruchaud Olivier 
Published: August 2015

Abstract
Autotaxin (ATX) through its lysophospholipase D activity controls physiological levels of lysophosphatidic acid (LPA) in blood. ATX is overexpressed in multiple types of cancers and we have shown previously that together with LPA generated during platelet activation promotes skeletal metastasis of breast cancer. However, the mechanisms that regulate the pathophysiological significances of the interactions between circulating LPA, ATX, and platelets remain undefined in cancer. Here we show that ATX is stored in α-granules of resting human platelets and released upon tumor cell-induced platelet aggregation, leading to the production of LPA. For this study, we used two human breast cancer cell lines (MDA-MB-231, MDA-B02) that do not express ATX. Our in vitro and in vivo experiments demonstrate that non-tumoral ATX controls the early stage of bone colonization by tumor cells and to a less extent osteolytic bone metastasis progression. Moreover, expression of a dominant negative integrin αvβ3-Δ744 or treatment with the anti human αvβ&;3 monoclonal antibody LM609 completely abolished binding of ATX to tumor cells, demonstrating the requirement of a fully active integrin αvβ3 in this process. The present results establish a new mechanism for platelet contribution to LPA-dependent metastasis of breast cancer cells and demonstrate the therapeutic potential of disrupting the binding of non-tumor-derived ATX with the tumor cells for the prevention of metastasis.
Citation Format: Raphael Leblanc, Sue-Chin Lee, Dereck Norman, Johnny Ribeiro, Gabor Tigyi, Olivier Peyruchaud. Non-tumoral autotaxin stored into platelet α-granules promotes breast cancer cell metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5209. doi:10.1158/1538-7445.AM2015-5209