bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 930: Role of DLK1 in sarcoma stem cells
Authors: Han Ilkyu , Ahn Sun Hee , Kim Han-Soo 
Published: July 2017

Abstract
Sarcoma is a rare form of cancer that comprises about 1% of all malignancies. A large proportion of deaths by sarcomas are caused by tumor metastasis, of which the biological basis remains obscure. A significant body of evidence suggests that only a small population of sarcoma cells possess the ability to initiate and maintain tumors. These tumor-initiating cells have the ability to self-renew, recapitulating the cellular heterogeneity of the original cancer, and thus are often referred as cancer stem like cells (CSLCs).Delta-like factor 1 (DLK1) was cloned in the preadipocyte cells 3T3-L1 cDNA library. Previous studies reported on the role of DLK1 in mesenchymal stem cell differentiation, adipogenesis, myogenesis, and osteoblastogenesis. It was reported that DLK1+ liver cancer cells have characteristics similar to those of CSLCs and that DLK1 could be a potential therapeutic target against the liver CSLCs. However, little is known about role of DLK1 in CSLCs of sarcoma. The mRNA (real time PCR) and protein (Western blot) expression of DLK1 from 13 sarcoma cell lines was examined. CSLCs from sarcoma cell lines were isolated using FACS with CD133 and sphere forming assay. The effect of DLK1 on sarcoma tumorigenesis was examined using cell proliferation and cell invasion assays by DLK1 siRNA treatment.Real-time PCR showed the increased expression of DLK1 mRNA in sarcoma cell lines. In particular, DLK1 mRNA was highly expressed in U2OS (osteosarcoma), SW872 (liposarcoma), A204 (rhabdomyosarcoma), and HS-SYII (synovial sarcoma) cells. We observed a reduction in cell proliferation and invasion in U2OS, A204, and sw872 cells treated with DLK1 siRNA. CSLCs were isolated from U2OS, A204, and sw872 by the FACS sorting method using the CD133, a CSLC marker in sarcoma. The number of active sarcoshperes in CD 133+ cells were significantly higher than that in CD133- cells by sphere forming assay. Soft agar assays revealed the presence of many more colonies in CD133+ cells than in CD133- or wild type cells. To investigate the effect of DLK1 on sarcoma CSLCs, sw872 cells were categorized into four groups: wild type, CD133-, CD133+ and spheres. Real-time PCR and western blot were used to detect the DLK1 gene in all four groups. We observed that DLK1 expression in sw872 CSLCs (CD133+ and spheres) were relatively low. We found that suppression of DLK1 by siRNA inhibited the invasiveness of CSLCs although it inhibited more effectively to activation of invasive cells as well as cell proliferation in sw872 non-CSLCs.These results suggest that DLK1 may play a role in tumorigenesis of CSLCs and cancer cells in various sarcomas.
Citation Format: Ilkyu Han, Sun Hee Ahn, Han-Soo Kim. Role of DLK1 in sarcoma stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 930. doi:10.1158/1538-7445.AM2017-930
Abstract 935: CD133+ cancer stem cells promoted by VEGF accelerate the recurrence of hepatocellular carcinoma
Authors: Chen Dexi , Liu Kai , Hao Meijun , Ouyang Yabo , Zheng Jiasheng , Challagundla Kishore Babu. 
Published: July 2017

Abstract
The function of cancer stem cells (CSCs) on inducing HCC recurrence after radiofrequency ablation (RFA) is still unclear. Here, 19 RFA-treated primary HCC patients were enrolled. We identified a dramatic increase of plasma VEGF in some patients (termed type II, n=9) after RFA, who suffered early HCC recurrence; the other patients (termed type I, n=10) had no increased plasma VEGF but had longer interval for HCC recurrence. Moreover, the expression of CSCs marker, CD133, was dramatically increased in recurrent HCC tissue of Type II in comparison with type I, suggesting induction of CD133+ CSCs may contribute to early HCC recurrence. In vitro studies demonstrated that VEGF stimulus enhanced the level of CD133+ CSCs and their self-renewal ability by inducing Nanog dependently on activation of VEGFR2. In vivo studies further demonstrated that CD133+ CSCs with VEGF stimulus formed larger tumor size in comparison with non-stimulus; and VEGF stimulus increased the tumorigenic cell frequency of primary HCC cells dependently on the presence of Nanog and VEGFR2. In recurrent HCC tissue of type II, but not type I, almost all CD133+ cells were Nanog and p-VEGFR2 positive cells, suggesting that activation VEGFR2 is critical for RFA-induced tumor stemness in HCC. Taken together, RFA-induced VEGF promotes tumor stemness and accelerates tumorigenesis in HCC dependently on Nanog and VEGFR2, which is valuable for the prediction of HCC recurrence after RFA and development of novel therapeutics.
Citation Format: Dexi Chen, Kai Liu, Meijun Hao, Yabo Ouyang, Jiasheng Zheng, Kishore Babu. Challagundla. CD133+ cancer stem cells promoted by VEGF accelerate the recurrence of hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 935. doi:10.1158/1538-7445.AM2017-935
Abstract 937: Plasticity in heterogenous cancer stem cells promotes glioblastoma radioresistance
Authors: Minata Mutsuko , Audia Alessandra , Shi Junfeng , Lu Songjian , Pavlyukov Marat , Gillespie Yancey Gillespie , Bhat Krishna , Nakano Ichiro 
Published: July 2017

Abstract
Some cancers including Glioblastoma (GBM) have hierarchical cellular architecture with cancer stem cells (CSCs) as a minor tumorigenic subpopulation. While CSCs have been touted to contribute to initiate recurrence, post-surgical therapy-induced phenotypic changes in CSCs remain elusive. Here we report that treatment of GBM cells with ionizing radiation (IR) promotes a wound-healing mesenchymal signature, accompanied by conversion of naïve CSCs expressing CD133 to post-treatment more radioresistant CSCs expressing the GPI-anchored, TGFb-inhibitory protein CD109 in an ATM, NF-kB, CEBP-b dependent manner. In post-IR GBM, these therapy-escaped CD133-/CD109+ GBM cells, but not the rest of the tumor, uniquely retain clonogenic, tumorigenic, and multi-potent capacities both in vitro and in vivo. CD109 silencing unexpectedly eliminates cancer stemness via controlling YAP/TAZ as the downstream target and this CD109-YAP/TAZ signaling axis is evolutionally conserved between drosophila and human brain tumors. Clinically, both CD133 and CD109 are independently associated with poorer prognosis of GBM patients, while the poorest prognosis group of GBM expressed both CD133 and CD109 at higher rates. These data indicate a possibility of the post-IR CSC plasticity and subsequent heterogeneity, and the activation of the CD109-YAP/TAZ signaling axis as previously unidentified therapeutic targets for post-IR recurrent GBM.
Citation Format: Mutsuko Minata, Alessandra Audia, Junfeng Shi, Songjian Lu, Marat Pavlyukov, Yancey Gillespie Gillespie, Krishna Bhat, Ichiro Nakano. Plasticity in heterogenous cancer stem cells promotes glioblastoma radioresistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 937. doi:10.1158/1538-7445.AM2017-937
Abstract 939: Single cell mRNA expression profiling reveals heterogeneity of normal and malignant breast stem cell populations
Authors: Fouladdel Shamileh , Colacino Justin , Azizi Ebrahim , Wicha Max S. 
Published: July 2017

Abstract
The normal breast contains epithelial populations which are hierarchically organized, a profile recapitulated in breast cancer. At the apex of these hierarchies are "stem like" cells defined by their capacity to self-renew as well as to generate more differentiated progeny. In breast cancer these "cancer stem cells" (CSCs) have been shown to be important mediators of tumor metastasis and treatment resistance. Although the phenotypes of normal rodent and human mammary stem cells have been characterized, CSC populations are operationally defined by their capacity for tumor initiation. In addition, putative breast CSC markers such as CD44+/CD24low/- and or ALDH+ have proven useful in enriching for cells capable of tumor initiation and previous studies have suggested that these markers identify alternative mesenchymal and epithelial stem cell states, respectively. However, it remains unclear whether CSCs exist in discrete states or whether these cells actually represent a continuum reflected in heterogeneity of cell populations defined by expression of these markers. To address this question we utilized single cell mRNA expression profiling of normal and malignant breast stem cells. We first generated a panel of 96 genes representing stem cell and developmental pathways and analyzed expression of these 96 genes utilizing Fluidigm’s C1 and BioMark HD technologies and TaqMan gene expression assays. We also utilized Fluidigm’s Polaris to selectively isolate single cells that were then analyzed by illumina RNA-Seq method. Utilizing these advanced technologies, we demonstrated that both normal and malignant breast stem cells characterized by CD44+/CD24low/- and or ALDH+ expression are highly heterogeneous. For example, the ALDH isoforms ALDH1A1 and ALDH1A3 were each expressed in some single cells and co-expressed in others. ALDH1A1 expressing single cells appeared to express a unique gene pattern characterized by SLIT/ROBO, PLXNA2, RHOU and HNF1a. These results suggest that at the level of mRNA expression, normal and malignant breast stem cells display a greater heterogeneity than has previously been reported. These results have important implications for breast carcinogenesis as well as for the development of therapeutic strategies designed to target CSCs in breast cancer.
Citation Format: Shamileh Fouladdel, Justin Colacino, Ebrahim Azizi, Max S. Wicha. Single cell mRNA expression profiling reveals heterogeneity of normal and malignant breast stem cell populations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 939. doi:10.1158/1538-7445.AM2017-939
Abstract 945: Oligodendrocytes might up-regulate the Invasiveness of glioblastoma cells via angiopoietin-2 signaling
Authors: Kawashima Toshiyuki 
Published: July 2017

Abstract
Background & Aims: Glioblastoma (GBM, WHO Grade IV) is considered as the most lethal neoplasm of all solid cancers due to its inherent intensive invasiveness. GBM may arise de novo, or following progression from lower grade gliomas. Recently, solid tumor progression has been recognized as the product of an evolving crosstalk between the cancer cells and its surrounding glial cells. The intensive invasion activity of GBM cells might be regulated by surrounding normal cells such as oligodendrocytes or fibroblasts. In this study, we evaluated the interactive factors between GBM cells and normal glial cells to determine the role of oligodendrocytes in regulating the invasiveness of glioblastoma cells.
Methods: Two GBM cell lines, T98G and U251, were used. Two oligodendrocyte cell lines, ODC1 and ODC2, were derived one each from surgical tissues of patients with low-grade glioma (WHO Grade II). Two fibroblasts cell lines, GF1 and GF2, were derived one each from surgical tissues of patients with GBM. Oligodendrocytes and fibroblasts were confirmed by immuno-histochemical staining. The invasive property of GBM cells was analyzed in the presence or absence of conditioned medium from oligodendrocytes or fibroblasts by wound-healing assay and Boyden chamber invasion assay. The proliferation ability of GBM cells was examined by MTT assay. Subsequently Cytokine array was used to examine the cytokines and growth factors in the conditioned medium from oligodendrocytes or fibroblasts.
Results: Oligodendrocyte cells, ODC1 and ODC2 cells, significantly (p&lt;0.01) increased the migration and invasion ability of GBM cells, T98G and U251. In contrast, fibroblasts, GF1 and GF2 cells, did not affect the migration and invasion ability of GBM cells. Cytokine array indicated that Angiopoietin-2 was found in the conditioned medium from oligodendrocytes, but not that from fibroblasts. Angiopoietin-2 significantly (p&lt;0.01) increased the invasiveness of GBM, but not their proliferation ability.
Conclusion: Oligodendrocytes might up-regulation of the invasiveness of GBM cells via angiopoietin-2 signaling pathway. Hence, angiopoietin-2 can be considered as a promising target for the treatment of malignant gliomas.
Citation Format: Toshiyuki Kawashima. Oligodendrocytes might up-regulate the Invasiveness of glioblastoma cells via angiopoietin-2 signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 945. doi:10.1158/1538-7445.AM2017-945
Abstract 946: Characterize and identify secreted high molecular weight heparanase from PC3M conditioned medium
Authors: Ju Donghong , Kosir Mary A. 
Published: July 2017

Abstract
Introduction: Neutrophils, platelets, lymphocytes are typical sources of NAP-2 which is associated with heparanase activity. Heparanase degrades polymeric heparan sulfate molecules into shorter oligosaccharides, participating in extracellular matrix degradation. It is active under acidic conditions during tumor invasion and inflammatory processes. Our lab previously found that some cell lines like androgen independent prostate cancer cells (PC3M) can secrete a protein that reacts with anti-NAP-2 antibody, but has a much higher molecular weight(&gt;50KD) than NAP-2 (MW~6-14 KD), and has heparanase activity. The purpose of this study is to characterize and identify this protein.
Procedures: Immunoprecipitation was performed using Pierce DirectIP kit according the manufacturer’s instructions. Heparin binding affinity column used HiTrap™ Heparin HP column from GE Healthcare Bio-Sciences. The binding buffer was 10mM NaAcetate pH 5.0, the eluting buffers were 0.5M-2M NaCl in 10mM NaAcetate pH 5.0. The mass spectrometry was done by KCI Proteomics Core facility.
Data: The immunoprecipitation method confirmed that this higher molecular weight protein indeed can be pulled down by the NAP-2 antibody, and after using heparin binding affinity column to purify, we can still get the &gt; 50KD band on the western blot for NAP-2, meaning it is a heparin binding protein.
Conclusions: A protein identified with NAP-2 antibody, but with higher molecular weight than native NAP-2 is found in the conditioned medium of PC3M cells that binds heparin, further confirming a potential role in tumor progression for prostate cancer.
Citation Format: Donghong Ju, Mary A. Kosir. Characterize and identify secreted high molecular weight heparanase from PC3M conditioned medium [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 946. doi:10.1158/1538-7445.AM2017-946
Abstract 948: Characterization of the microenvironment of murine primary triple negative breast cancer
Authors: Balestrieri Kassondra , Pittman Keith , Ramez Mohamed , Vohra Nasreen , Verbanac Kathryn 
Published: July 2017

Abstract
The purpose of this study was to investigate the role of inflammatory cells in the metastatic process using reliably metastatic murine models of Triple Negative Breast Cancer (TNBC). We have previously selected, developed and characterized two reliably metastatic TNBC mouse models for our investigations. The T11 (claudin-low) and 2225LM (basal-like) Balb/c-derived transplantable tumors display molecular profiles that mirror human TNBC. Here we report characterization of the inflammatory cells and microenvironment in these primary TNBC tumors and at metastatic sites in both heterotopic and orthotopic models. Tumors were implanted in the s.c. flank or mammary fat pad and resected 1-2 weeks later to promote the growth of seeded metastases, when volumes reached ~700 mm3 or 300 mm3, respectively. Both flow cytometric analysis and immunohistochemistry of primary tumors demonstrated high infiltration by myeloid-derived cells (CD11b+) and low levels of lymphoid cells (CD3+). Myeloid cells were also the major infiltrating cells in lung metastases and were significantly elevated compared to normal lung. The granulocytic subset (CD11b+Ly6G+) predominated, consistent with an immunosuppressive role for cells with this phenotype (N2, G-MDSC, etc.). Primary 2225LM and T11 tumors and metastatic lung tumor homogenates were assayed for immunomodulators and compared to normal breast and lung tissue from age-matched contemporary controls. G-CSF was significantly increased in tumors and levels (pg/mg protein) were correlated with tumor burden. VEGF was significantly elevated in all tumors, as were chemoattractants for granulocytic cells (KC/CXCL1, MIP-2/CXCL2), monocytic cells (MCP-1/CCL2), eosinophils (Eotaxin/CCL11) and T cells (MIG/CXCL-9). In the heterotopic model, lung levels of KC/CXCL1 and MCP-1/CCL2 were significantly increased prior to frank lung metastasis (5-30 days post-implant). These data suggest that TNBC-derived G-CSF may play a role in the mobilization of CD11b+Ly6G+ granulocytes and progenitors from the bone marrow and key chemokines may mediate migration of these cells to metastatic sites. Future studies will define phenotypic and functional characteristics of the G-MDSC that are promoting tumor progression in these murine TNBC models.
Citation Format: Kassondra Balestrieri, Keith Pittman, Mohamed Ramez, Nasreen Vohra, Kathryn Verbanac. Characterization of the microenvironment of murine primary triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 948. doi:10.1158/1538-7445.AM2017-948
Abstract 949: Resistin potentiates stemness and chemoresistance of breast cancer cells through STAT3 activation: implications in breast cancer health disparity
Authors: Deshmukh Sachin Kumar , Bhardwaj Arun , Srivastava Sanjeev K. , Tyagi Nikhil , Al-Ghadhban Ahmed , Singh Ajay P. , Dyess Donna L. , Carter James E. , Singh Seema 
Published: July 2017

Abstract
Breast cancer (BC) is most frequently diagnosed cancer and remains the second leading cause of cancer-related deaths in women in the United States. African American (AA) women bear an additional burden of BC with early onset of disease, poorer prognosis, higher risk of recurrence, and worst clinical outcome as compared to Caucasian American (CA) women. Emerging evidence strongly argue the role of tumor-microenvironment (TME) in BC of AA and CA racial backgrounds. On the similar line, our earlier findings suggested that serum levels of resistin; an inflammatory cytokine are significantly elevated in AA BC patients compared to their CA counterparts. Furthermore, we demonstrated that resistin promoted growth and aggressiveness of BC cells. In the present study, we investigated the role of resistin in stemness and chemoresistance of BC cells. For this, two BC cells of CA (MDA-MB-231) and AA (MDA-MB-468) origin were treated with resistin and sphere-forming ability, a key characteristic of cancer stem cells, was determined. Data demonstrate that number of spheres is significantly enhanced in both the BC cells upon resistin stimulation. Immunoblot analyses reveal that resistin-induced sphere-forming ability is associated with enhanced levels of stemness-associated transcription factors (Nanog and KLF4) in BC cells. We next examined if resistin conferred chemoresistance to BC cells. Our data suggest that resistin-treated MDA-MB-231 and MDA-MB-468 BC cells develop greater resistance against doxorubicin-induced cytotoxicity. Notably, the effects conferred by resistin were more prominent in AA BC cells comparing to CA BC cells. Our mechanistic studies unveiled an important role of STAT3 activation in the resistin-induced stemness and chemoresistance of BC cells. Taken together, our findings provide novel insight into the role of resistin in BC biology and further strengthen its role in racially disparate clinical outcomes.
Citation Format: Sachin Kumar Deshmukh, Arun Bhardwaj, Sanjeev K. Srivastava, Nikhil Tyagi, Ahmed Al-Ghadhban, Ajay P. Singh, Donna L. Dyess, James E. Carter, Seema Singh. Resistin potentiates stemness and chemoresistance of breast cancer cells through STAT3 activation: implications in breast cancer health disparity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 949. doi:10.1158/1538-7445.AM2017-949
Abstract 950: Involvement of proinflammatory chemokine network between adipocytes and triple negative breast cancer cells
Authors: Ignacio Rosa Mistica Coles , Choi Hyeongjwa , Gibbs Carla , Lee Eunsook , Adunyah Samuel , Son Deok-Soo 
Published: July 2017

Abstract
Obesity has become a global epidemic and causes a chronic low-grade inflammation. This poses a large health burden because excess adiposity can lead to chronic diseases such as type 2 diabetes, cardiovascular disease and some cancers. Obese individuals get higher incidence, progression and mortality of cancers compared to lean ones. Particularly, breast cancer (BC) in women is closely associated with obesity. Despite an epidemiological link between obesity and low cancer survival rates, little is known about the molecular mechanisms by which obesity promotes BC progression. Obesity-derived chronic low-grade inflammation involves alteration of a chemokine network that may contribute to the cancer progression and metastasis. Herein, we proposed the novel concept that the chemokine network between obesity and BC builds an inflammatory burden via proinflammatory chemokines to promote cancer progression. We employed mesenchymal BC cell PY8119 and epithelial-like BC PY230 for triple negative BC (TNBC) cell model, and mouse 3T3-L1 preadipocyte and adipocyte conditioned media (CM) to mimic lean and obese conditions in vitro. We examined the profiles of chemokine signature of PY8119 and PY230 treated with preadipocytes and adipocytes CM using PCR array. Both preadipocytes and adipocytes CM-treated PY8119 and PY230 cells absent or low levels in chemokine receptors. On the other hand, the chemokines CCL2, 5, 7 and CXCL10 showed higher expression in both preadipocyte and adipocyte CM-treated PY8119. Interestingly, adipocyte CM-treated PY8119 cells dominantly expressed CXCL1-3 compared to preadipocyte CM-treated cells. In addition, CCL2, 5, 7, 20, and CXCL1, 5, 10 were highly expressed in both preadipocyte and adipocyte CM-treated PY230 cells. Moreover, CXCL2 and 3 were significantly induced in PY230 cells after treatment with adipocyte CM compared to preadipocyte CM. Taken together, the results indicate that dominant chemokines CXCL1-3 expressed in adipocyte CM-treated TNBC cells promote a pro-tumor inflammatory network. Hence, these proinflammatory microenvironment augmented by adipocytes might contribute to TNBC progression.
Citation Format: Rosa Mistica Coles Ignacio, Hyeongjwa Choi, Carla Gibbs, Eunsook Lee, Samuel Adunyah, Deok-Soo Son. Involvement of proinflammatory chemokine network between adipocytes and triple negative breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 950. doi:10.1158/1538-7445.AM2017-950