bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1559: CCR5-CCRL2 regulates CCL5-induced organ specific metastasis: the in vitro and in vivo studies
Authors: Hsieh Chia-Ling , Liu Che-Ming , Sung Shian-Ying 
Published: July 2016

Abstract
Previous studies of soluble factors in the tumor associated stromal cells demonstrated the elevation of CCL5 expression in prostate cancer patient sera that correlated wit malignant cancer progression. To evaluate the expression level of chemokine receptors in response to chemokines released by reactive stroma, quantitative PCR to evaluate the mRNA level of chemokine receptors was performed. We noticed the significant increased of CCRL2 (86-fold) and CXCR4 (45-fold) in androgen independent prostate cancer (AIPC) cells. This increased of CCRL2 expression also confirmed in malignant lung, breast and rental cells. Knockdown of CCRL2 declined 75% of migration activities induced by CCL5, suggests CCRL2 involve in CCL5 induce cancer migratory activities (t-test, p&lt;0.001). IHC analysis of CCRL2 in paired prostate cancer patients was performed and revealed increasing of CCRL2 expression in malignant prostate cancer locus, whereas no CCRL2 can be detected in the benign region of same patient. Proximity ligation assays (PLAs) of benign, high grade tumor and tissues collected from patients less than 5-year survive demonstrated the PLA signals only in the lethal progression on patients. In vivo xenograft mice model studies demonstrated the organ specific cancer metastasis can be enhanced after overexpressed CCRL2 in cancer cells. Molecular analysis of CCRL2 demonstrated that CCRL2 regulated EZH2 expression in prostate cancer cells. In summary, out studies indicated the increased expression of CCRL2 play a central role in cancer cell migration induced by chemokine CCL5. The released of CCL5, secreted by bone stromal cells after interaction with dormancy cancer cell, may induce directional migration and invasion of circulating cancer cells. Clinical analyses demonstrated increased of CCRL2 in malignant prostate cancer. Inhibition of these homing mechanisms might significantly decreased cancer cell metastatic activities of AIPC patients.
Citation Format: Chia-Ling Hsieh, Che-Ming Liu, Shian-Ying Sung. CCR5-CCRL2 regulates CCL5-induced organ specific metastasis: the in vitro and in vivo studies. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1559.
Abstract 1575: Intratumoral injection of interleukin-17 inhibits distant metastasis of radiation-induced recurrent tumor
Authors: Li Yi-Nan , Chen Fang-Hsin , Hong Ji-Hong , Chiang Chi-Shiun 
Published: July 2016

Abstract
Interleukin-17 (IL-17) is a pro-inflammatory cytokine that leads to the production of GM-CSF, G-CSF, IL-1, IL-6, TNF-α. It can be secreted by various cells, including T cells, NKT cells, fibroblasts, and even tumor cells. In addition, reports have shown that IL-17 could also promote tumor growth by recruiting and expanding granulocytic myeloid suppressor cells (G-MDSCs). In our preliminary study, we found that Tramp-C1, a murine prostate cancer cell line, had remarkable IL-17 level when it grew in pre-irradiated (PreIR) stroma. In contrast, B16F0, a murine melanoma cell line, had much less IL-17 and stronger tumor bed effect, in terms of tumor growth delay, but lung metastasis were formed gradually as B16F0 developed. When the recombinant IL-17 was directly injected into the B16F0 tumors growing in PreIR stroma, we found that the probability of lung metastasis was decreased despite a slight increase of tumor growth at primary site. This indicates that IL-17 may have different effects on irradiated tumor bed and distant metastatic site. The influence of IL-17 on tumor microenvironments of distant metastatic sites and irradiated tumor bed is currently under investigation. In conclusion, we propose a new therapeutic approach of reducing distant metastasis following radiation therapy.. This work was kindly supported by MOST-104-2314-B-182 -024 grant to Fang-Hsin Chen.
Citation Format: Yi-Nan Li, Fang-Hsin Chen, Ji-Hong Hong, Chi-Shiun Chiang. Intratumoral injection of interleukin-17 inhibits distant metastasis of radiation-induced recurrent tumor. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1575.
Abstract 1593: Stat3 signaling in erbB3-mediated epithelial-mesenchymal transition in erbB2-positive breast cancer cells
Authors: Lyu Hui , Wu Ying , Zhou Yan , Liu Bolin 
Published: July 2016

Abstract
Introduction: Understanding the mechanism of metastatic program is essential to reducing the mortality of cancer patients. It is well known that epithelial-mesenchymal transition (EMT) contributes to cancer metastasis. Recently, numerous studies have documented the role of erbB3-mediated oncogenic signaling in breast cancer progression. In this study, we have focused on investigating the effect of Stat3 activation on EMT-induced by erbB3 receptor in erbB2-positive (erbB2+) breast cancer cells.
Methods: Immunofluorescence analyses were performed to study the localization and expression of EMT markers in erbB2+ breast cancer cells. Lentiviral vector containing shRNA was used to specifically knockdown erbB3. Western blot analyses were performed to assess the expression and activation of proteins. Cell growth (MTS) assays were used to determine cell viability. Wound healing and transwell assays were used to examine the motility and migration of cells.
Results: We discovered that ectopic expression of erbB3 facilitated EMT, as evidenced by change of cell morphology, induction of mesenchymal markers Vimentin, Snail, Slug, ZEB1 and repression of the epithelial marker E-cadherin in erbB2+ breast cancer cells. Wound healing and transwell assays indicated that the capability of cell motility and migration was enhanced. In contrast, specific knockdown of erbB3 abrogated the observations described above. Moreover, elevated expression of erbB3 potently stimulated activation of Stat3, which has been validated to act as a promoter of tumor invasion and metastasis in many type cancers. Suppression of Stat3 signaling via its inhibitor, S3I-201, significantly alleviated EMT and cell motility/migration that were triggered by activation of erbB3. To further assess the clinical relevance of erbB3 signaling in cancer metastasis, we took advantage of a publicly accessible portal that allows analysis of the effect of genes on survival using 4,142 breast cancer samples (http://kmplot.com/analysis/). Kaplan-Meier survival curves showed that the erbB2+ breast cancer patients with erbB3-high expression tended to have a shorter Distance Metastasis-free Survival (DMFS).
Conclusion: Activation of Stat3 signaling by erbB3 promotes EMT and shifts the cellular phenotype toward a mesenchymal state that is advantageous for cancer metastasis. Our data shed a new sight on erbB3's role in erbB2+ breast cancer metastasis and may facilitate the development of novel strategy for treatment of tumor progression.
Keywords: ErbB3, Stat3, EMT, Metastasis, Breast Cancer
Citation Format: Hui Lyu, Ying Wu, Yan Zhou, Bolin Liu. Stat3 signaling in erbB3-mediated epithelial-mesenchymal transition in erbB2-positive breast cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1593.
Abstract 160: Identification of the carcinoma and immune cells in the breast cancer by single-cell RNA sequencing
Authors: Chung Woosung , Eum Hye Hyeon , Kim Kyu-Tae , Lee Kyung-Min , Jo Arum , Han WonShik , Lee Hae-Ock , Park Woong-Yang 
Published: July 2016

Abstract
Summary: Breast cancer is a heterogeneous type of cancer accompanying extensive immune cell infiltration. Although its mortality rate has been decreasing with early diagnosis and introduction of molecular targeted therapies, it is still one of the world leading cause of cancer death in women. In breast cancer, molecular subtyping is used for the patient stratification and treatment decisions, emphasizing the importance of inter-patient tumoral heterogeneity in the tumor cell behavior. Tumor cells within a patient may also manifest intra-tumoral heterogeneity, which may cause treatment resistance. Single cell gene expression profiling would reveal both inter- and intra-tumoral heterogeneity in breast cancer encompassing tumor cells and associated stromal and immune cells.
Experimental Process: From 4 different subtype primary breast cancer and 2 lymph node metastases, single cells were captured and amplified through C1™Single-cell Auto Prep System (Fluidigm) with the SMARTer Ultra Low RNA Kit. Sequencing libraries were constructed with the Nextera XT DNA sample Prep Kit and sequenced through a Hiseq2500 (Illumina) as 100-bp paired end mode of the TruSeq Rapid PE Cluster kit and Truseq Rapid SBS kit.
Computational Process: RNA sequencing reads were aligned to the modified human genome reference using 2-pass mode of STAR_2.4.0b, and transcript per million (TPM) values were obtained as the relative gene expression levels of single cells through RSEM v1.2.17.
Results: As most breast cancers originate from the mammary epithelium, we distinguished carcinoma cells from associated non-tumor cells by epithelial cell adhesion molecule (EPCAM) signature genes. We validated the distinction with chromosomal gene expression patterns and gene set enrichment analyses using tumor, stromal, or immune genesets. With or without removal of non-tumor cells, TNBC tumor cells showed the highest gene expression heterogeneity, recapitulating the known inter-patient heterogeneity. TNBC tumor cells from a single patient were categorized into 6 different TNBC-subtypes, further demonstrating intra-tumoral heterogeneity. In addition, immune cells identified in the TNBC tumor were naïve B cells and regulatory T cells, suggesting non-activated status of the immune system.
Conclusions: The high resolution gene expression profiling revealed features of breast cancer transcriptome which may provide clues for molecular directed therapies targeting the tumor or the immune compartment.
Citation Format: Woosung Chung, Hye Hyeon Eum, Kyu-Tae Kim, Kyung-Min Lee, Arum Jo, WonShik Han, Hae-Ock Lee, Woong-Yang Park. Identification of the carcinoma and immune cells in the breast cancer by single-cell RNA sequencing. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 160.
Abstract 1603: Highly expressed integrin-α8 in multiple myeloma early relapse induces epithelial to mesenchymal transition-like features
Authors: Ryu Jiyeon , Koh Youngil , Lee Hyun Jung , Chung Hyun Sub , Yoon Sung-Soo 
Published: July 2016

Abstract
Multiple myeloma (MM) is characterized by clonal proliferation of malignant plasma cells in the bone marrow niches. Despite the remarkable advances of treatment for MM,still many patients of MM struggle early relapses and its mechanism is not well understood. Patients with early relapse after autologous bone marrow transplantation need to be biologically characterized to better understand and reach complete remission. To define altered gene expression in MM relapse, we performed microarray with whole bone marrow aspirates from 16 relapsed MM patients who underwent auto-BMT. Gene expression profile was compared (P &lt; 0.01) and divided into two groups on the basis of their progression-free survival (PFS) at the point of 12 months. To discern the significance of the result, only four patients with shortest and longest duration of PFS was also nexamined, and interestingly both of the analysis showed common up-regulated genes including PDGFB, ITGA7, and ITGA8. Their associated pathways were focal adhesion, ECM-receptor interaction, and regulation of actin cytoskeleton (P &lt; 0.05). By performing qRT-PCR, we validated three genes and only ITGA8 was corresponded with microarray data that early relapsed patients showed higher expression of ITGA8. Several integrin family members are well documented to involve in MM progression that it mediates MM cell adhesion, migration and homing through BM microenvironment. However, integrin-α8 is largely unknown in MM. Due to ITGA8 was highly expressed in MM relapse, we functionally overexpressed integrin-α8 in MM cell lines. Surprisingly, it activated genes showing stem-like features including HIF1a, VEGF, OCT4, and Nanog and EMT-related genes, such as N-cadherin, Slug, Snail and CXCR4. These, consequently enhanced invasion and migration abilities and reduced adhesion activity, indicating the mechanism of MM progression, metastasis as well as relapse. Our speculated specific gene, integrin-α8, up-regulated in MM early relapse, regulates EMT feature in MM that suggesting a potential marker for relapse and attractive clinical target to achieve complete remission.
Citation Format: Jiyeon Ryu, Youngil Koh, Hyun Jung Lee, Hyun Sub Chung, Sung-Soo Yoon. Highly expressed integrin-α8 in multiple myeloma early relapse induces epithelial to mesenchymal transition-like features. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1603.
Abstract 161: Single-cell RNA sequencing presents explicit expression signatures in primary breast cancer
Authors: Eum Hye Hyeon , Lee Hae-Ock , Chung Woosung , Kim Kyu-Tae , Lee Kyung-Min , Jo Arum , Han WonShik , Park Woong-Yang 
Published: July 2016

Abstract
Intratumoral heterogeneity has emerged as a problem to be resolved for precise diagnosis and effective treatment of cancer. Breast cancer is one of the most heterogeneous cancer in its molecular subtypes and its intratumoral genomic diversity has been demonstrated as well. Single-cell sequencing approach would reveal heterogeneity in gene expression signatures and the common gene expression characteristics across tumor cells within a tumor. In this study, we isolated live individual cells and amplified cDNAs using C1™Single-cell Auto Prep System (Fluidigm) then performed RNA sequencing using HiSeq2500 System (Illumina). Single-cell transcriptomes were acquired from four primary tumor (ER+/HER2-, ER-/HER2+, ER+/HER2+ and triple negative breast cancer) and two matched lymph node metastases (ER+/HER2+ and triple negative breast cancer). Because the tumor tissue isolates may include stromal and immune cells in the tumor microenvironment, we defined ‘epithelial cell adhesion molecule signature’ to filter out non-tumor populations (Poster# presented by Woosung Chung et. al) After the removal of non-tumor cells, collected tumor single-cell transcriptomes largely recapitulated bulk tumor-expression profiles. The ER+/HER2- tumor cells showed highly activated estrogen receptor-associated pathways. Although both ER-/HER2+ and ER+/HER2+ tumors had the HER2 gene amplification and overexpression, HER2/HER3 pathway is activated only in ER-/HER2+ tumor cells. The association of gene expression for cancer stem cells and chemoresistance, such as IL8 and CXCL1, with HER2/HER3 signaling pathway activation was prominent. By contrast, the ER+/HER2+ tumor cells had highly activated estrogen receptor signaling, presenting them as the luminal type. The triple negative breast cancer cells highly expressed adhesion molecules and proteases suggesting their invasive nature, yet demonstrated extensive gene expression heterogeneity. Collectively these data revealed the power of single cell gene expression profiling in the precise characterization of tumor cell properties. The explicit gene expression signatures for patient specific tumors may be defined as subtype-specific signatures and helpful to unmask targets for molecular directed therapies.
Citation Format: Hye Hyeon Eum, Hae-Ock Lee, Woosung Chung, Kyu-Tae Kim, Kyung-Min Lee, Arum Jo, WonShik Han, Woong-Yang Park. Single-cell RNA sequencing presents explicit expression signatures in primary breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 161.
Abstract 1630: Dysregulation of Hippo pathway in metastatic prostate cancer
Authors: Huang Jen-Ming , Chu Gina C-Y , Kim Hyung L. , Zhau Haiyen E. , Chung. Leland W.K. 
Published: July 2016

Abstract
Background: Prostate cancer (PCa) is prevalently diagnosed and more than 80% of late stage PCa patients develop bone metastases. We hypothesized that the selective lodging of the PCa cells in the bone can be contributed by increased RANK-mediated cell signaling network. Cancer cell-derived RANKL orchestrates a complex bone-remodeling program facilitating PCa bone colonization through the activation of specific transcription factors (TFs) promoting PCa-bone microenvironment interaction through increased epithelial to mesenchymal transition (EMT), cell growth, and osteomimicry. Overexpression of RNAKL in indolent LNCaP cells drives cancer bone and soft tissue metastases.
Methods and Results: Microarray gene expression was performed to compare RANKL- and Neo-vector- transfected LNCaP cells, LNCaPRANKL and LNCaPneo, respectively. qRT-PCR and western blot were performed to confirm the expression of RANKL-targeted genes in these cells. We found the new extracellular diffusible signal mediated by RANKL, regulating Hippo pathway in the aggressive PCa cells. Recombinant RANKL-treated indolent PCa cells, LNCaP and LAPC4, were shown to gain increased aggressiveness. The RANKL-treated indolent PCa cells exhibited down-regulation of Hippo pathway core kinases (Mst1/2 and Lats1/2) but up-regulation of YAP/TAZ expressions. By deleting downstream effectors of Hippo pathway, YAP/TAZ, interrupted the aggressive PCa cells to migrate, proliferate and invade and reversed their EMT phenotype. Inhibitions of YAP/TAZ in aggressive PCa cells via genetic knockdown approach resulted in E-cadherin increase and Vimentin decrease. With the identification of crosstalk between Hippo and TGF-β, or Wnt pathways, this opened up a new network and targeting opportunity for PCa bone metastasis. The metastatic PCa cells with YAP/TAZ deletions were illustrated for sensitization to other therapeutic agents such as TGF-β inhibitors. These results prompted us to study the mechanism, validate the functional significance, and devise potential targeting strategies of Hippo pathway in PCa bone metastasis.
Conclusions: Our results showed that dysregulated Hippo pathway in the aggressive PCa cells. With deletions of YAP/TAZ, PCa metastatic abilities were inhibited. Our findings might explain why PCa cells prefer bone as primary metastatic sites. In addition, targeting YAP/TAZ could be a potential therapy for PCa bone metastasis.
Citation Format: Jen-Ming Huang, Gina C-Y Chu, Hyung L. Kim, Haiyen E. Zhau, Leland W.K. Chung. Dysregulation of Hippo pathway in metastatic prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1630.
Abstract 1641: Complex behavior of ALDH1A1 and IGFBP1 in liver metastasis of colorectal cancer
Authors: Kim Jin Cheon , Ha Ye Jin , Tak Ka Hee , Roh Seon Ae , Kim Chan Wook , Kim Tae Won , Cho Dong-Hyung , Kim Seon-Kyu , Kim Seon-Young , Kim Yong Sung 
Published: July 2016

Abstract
The present study aimed to identify upregulated genes associated with colorectal cancer (CRC) liver metastasis (CLM) using our dataset (GSE50760) previously established by RNA sequencing and to verify their biological behavior. Candidate genes were assessed for their role in tumor proliferation, invasion, and the expression of epithelial-mesenchymal transition/CRC stem cell (EMT/CSC)-related molecules. The role of the identified genes in CLM was verified in mice after intrasplenic transplantation of CRC cells. Of nine candidate genes, ALDH1A1 and IGFBP1 were selected and showed few post-translational changes. The upregulation of ALDH1A1 and IGFBP1 significantly and time-dependently decreased cell proliferation (p ≤ 0.001-0.003) and suppressed invasiveness by ≥3 fold over control cells (p &lt; 0.001) in the SW480 cell line, whereas it had a mild effect on reducing SW620 cell proliferation. EMT/CSC-related molecules showed different patterns of expression in CLM tissues and treated CRC cells. The cadherin switch, namely, N-cadherin upregulation with E-cadherin downregulation, was not observed in CLM tissues and treated CRC cells. Persistent overexpression of β-catenin, vimentin, and ZO-1 in IGFBP1-overexpressing SW480 cells may have contributed to CLM development in mice implanted with IGFBP1-overexpressing cells (CLM occurrences: SW480/IGFBP1 transfected mice vs. SW480/vector and /ALDH1A1 transfected mice, 4/8 vs. 0/10, p = 0.023). ALDH1A1 and IGFBP1 were differentially overexpressed in CLM and may play a dual role, functioning as tumor suppressors and metastasis promoting genes in CRC. Unidentified behaviors of these genes may facilitate the reassessment of their potential value as CLM modulators and as therapeutic targets.
Citation Format: Jin Cheon Kim, Ye Jin Ha, Ka Hee Tak, Seon Ae Roh, Chan Wook Kim, Tae Won Kim, Dong-Hyung Cho, Seon-Kyu Kim, Seon-Young Kim, Yong Sung Kim. Complex behavior of ALDH1A1 and IGFBP1 in liver metastasis of colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1641.