bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5018: Evidence for a dynamic interaction between bone marrow and the cutaneous epithelium during skin carcinogenesis by exposure to solar ultraviolet radiation.
Authors: Morris Rebecca J. , Readio Nyssa AK , Singh Ashok , Singh Anupama 
Published: August 2014

Abstract
Non-melanoma skin cancer induced by solar ultraviolet radiation (UV) is the most common of epithelial cancers and occurs more frequently in the human population than any other type of malignancy. Therefore, determining its etiology is a significant problem. The objective of this investigation was to determine whether there might be an interaction between epidermal keratinocytes and bone marrow during carcinogenesis induced by solar UV. First, we determined that bone marrow cells were recruited to the cutaneous epithelium where a subpopulation assumed epithelial characteristics during chronic exposure of mice to solar UV radiation. Second, we documented the presence of keratins in blood and bone marrow prior to and during exposure of mice to solar UV radiation by quantitative real time polymerase chain reaction, fluorescence activated cell sorting of freshly harvested cells, and by immunofluorescence microscopy of bone marrow smears. We observed low, but reproducible levels of keratins 8, 14 and 15 in both blood and bone marrow of un-irradiated mice, with a relatively higher expression of keratin 8 in blood, and a relatively higher expression of keratins 14 and 15 in bone marrow. Third, during chronic exposure to solar UV, we detected a dose dependent increase in the percentage of cells expressing keratin 14 in bone marrow: increasing from approximately 1% in un-irradiated control bone marrow, to approximately 10% after 10 weeks of irradiation, with greater increases at later time points. Surprisingly, this increase in keratin expression in bone marrow began many weeks prior to development of benign or malignant cutaneous neoplasms. Fourth, because these results could suggest a possible egress of keratinocytes from the cutaneous epithelium and homing to the bone marrow, we performed in vitro keratinocyte migration assays with bone marrow as bait. We observed a significant and reproducible migration of epidermal keratinocytes towards bone marrow over controls such as 3T3 cells, fetal bovine serum, or other keratinocyte cultures. We conclude from these studies that there is a dynamic interaction between the cells of the cutaneous epithelium and the bone marrow. The cells and the mechanisms involved in this interaction are currently under investigation.
Citation Format: Rebecca J. Morris, Nyssa AK Readio, Ashok Singh, Anupama Singh. Evidence for a dynamic interaction between bone marrow and the cutaneous epithelium during skin carcinogenesis by exposure to solar ultraviolet radiation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5018. doi:10.1158/1538-7445.AM2013-5018
Abstract 5019: Stem cell and neuroendocrine cell phenotypes of normal and malignant colonic cells.
Authors: Modarai Shirin R. , Opdenaker Lynn M. , Boman Bruce M. 
Published: August 2014

Abstract
In the development of colorectal cancer (CRC), stem cell (SC) overpopulation underlies tumor initiation and progression, but the underlying mechanisms are poorly understood. We hypothesized that neuroendocrine cells (NE) cells play a key role in maintaining the SC population in the normal colon and, aberrant signaling from NE cells contributes to tumor initiation and increased stemness. Indeed, NE cells and SCs reside in close proximity to each other in the SC niche at the bottom of the normal human colonic crypt. Therefore, it seems feasible that the communication between NE cells and SCs is crucial to normal crypt homeostasis and that dysregulation of the interactions between the two cell types could lead to SC overpopulation during cancer progression. Our studies on human colonic tissues show that in normal crypts, most cells (&gt;80%) expressing the colonic SC marker ALDH1 co-express NE markers such as chromogranin-A (CGA). Neither ALDH1+ nor CGA+ cells co-stained for markers for proliferating cells. Thus, in normal crypts, many ALDH1+ cells have NE characteristics (likely representing progenitor NE cells). In APC mutant crypts, the size of the undifferentiated SC population (ALDH+/CGA-) progressively increased relative to the size of the NEC population (both ALDH1+/CGA+ and ALDH1-/CGA+) during the stepwise progression to cancer. The distributions of these populations also extended father up the crypt (outside the normal SC niche). To evaluate how NE factors might regulate SCs, we did further studies to assess how NE factors might be regulating SCs. Because we found, by flow cytometric analysis, that various CRC cell lines (COL0320, DiFi, LoVo, SW480, HCT116 & HT29) each maintains a unique proportion of SCs and NE cells over time, we surmised these proportions are maintained constant through feedback mechanisms involving SC and NEC subpopulations. When these cell lines were induced to differentiate along the NE lineage upon retinoid treatment, they showed a decrease in the proportion of ALDEFLUOR+ cells and an increase in NE cell differentiation and enhanced collagen IV production. Retinoid treatment to induce NE differentiation also decreased the sphere-forming ability in terms of the number and sizes of spheres that were formed from each cell line. Taken together, our findings indicate that: (1) NE factors contribute to colonic SC regulation via an autocrine or paracrine mechanism in normal colon, and (2) dysregulation of these mechanisms contributes to colon cancer development.
Citation Format: Shirin R. Modarai, Lynn M. Opdenaker, Bruce M. Boman. Stem cell and neuroendocrine cell phenotypes of normal and malignant colonic cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5019. doi:10.1158/1538-7445.AM2013-5019
Abstract 5020: Characterization of epidermal stem cells in SKH1 hairless mice, a widely used mouse model to investigate ultraviolet radiation carcinogenesis.
Authors: Singh Ashok , Singh Anupama , Verma Ajit K. 
Published: August 2014

Abstract
Human cutaneous squamous cell carcinoma (SCC) is the second most common type of non-melanoma skin cancer (NMSC) after basal cell carcinoma (BCC) in US. Evidence indicates that the precursor cells are the precursor cells for the origin of SCC. The SCCs probably arise from bulge stem cell niche of hair follicle but not from the transit amplifying cells of epidermis. The SKH1 hairless mice is a widely used mouse model for ultraviolet radiation (UV)-induced carcinogenesis. However, SKH1 mice have never been evaluated for status of skin stem cell probably due to absence of hair and other associated hairless phenotype. It has recently become possible to isolate living hair follicle stem and progenitor cells from mouse skin because of the discovery of cell surface marker (CD34) that facilitate enrichment. The cell surface protein CD34, more widely known as a hematopoietic stem and progenitor cell marker, was found to be uniquely expressed in the mouse hair follicle bulge region using immunohistochemistry staining techniques. In addition, CD34 expression was restricted to the hair follicle regardless of hair follicle stage, making this a potentially important tool for selected enrichment of hair follicle bulge region keratinocytes. In combination with alpha 6-integrin staining and fluorescence activated cell sorting (FACS), CD34 is used to successfully isolate a small population of CD34+/alpha 6-integrin+ cells from a single cell preparation of mouse keratinocytes. CD34-expressing keratinocytes were confirmed to have properties consistent with stem and progenitor cells in that they were shown to be slowly cycling and have a high proliferative capacity in culture, growing larger colonies relative to those from CD34− keratinocytes. In the present experiments, the SKH1 mouse skin stem cell population was identified using stem cell markers (CD34+/α6-integrin+, Keratin-15, Gli1, and Sox9). The results of FACS analysis of live cells, isolated from untreated SKH1 mouse skin, indicate that there are 0.23% CD34+ and 1.05% CD34+/α6-integrin+ cells. The FACS sorted double positive (CD34+/α6-integrin+) stem cells of SKH1 are also observed to be positive for K15, Gli1, and Sox9 markers of stem cells in cytospin slides. In summary, the quantitative FACS analysis and qualitative immunofluorescence data in skin tissues confirms the presence of the stem cell populations in SKH1 mice. Support: (RO1CA102431).
Citation Format: Ashok Singh, Anupama Singh, Ajit K. Verma. Characterization of epidermal stem cells in SKH1 hairless mice, a widely used mouse model to investigate ultraviolet radiation carcinogenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5020. doi:10.1158/1538-7445.AM2013-5020
Abstract 5024: Epigenetic regulation of cancer stem cell states in a p53/PTEN inactivated mammary epithelial cells.
Authors: Ouzounova Maria , Davis April , Kim Gwangil , Malik Fayaz , Quraishi Ahmed A. , Clouthier Shawn G. , Wicha Max S. , Korkaya Hasan 
Published: August 2014

Abstract
Inactivation of the tumor suppressors, TP53 and PTEN in pre-neoplastic lesions has been implicated in tumor progression as well as in regulation of normal and malignant stem cell self-renewal. Down regulation of both p53 and PTEN in non-transformed MCF10A cells synergized to expand the cancer stem cell compartment transforming these cells and generating an EMT phenotype in vitro which generated highly metastatic tumors when injected in NOD/SCID mice.
These tumors could be fractionated based on their expression of CD49f and EPCAM. Gene expression analyses of these sub-fractions demonstrate an EMT gene signature in CD49f+/EPCAM- and CD49f-/EPCAM- cell populations. These findings are also supported by DNA methylation analyses. Although CD49f+EPCAM+ cell population express epithelial (MET) gene signature, these cells also generate tumors in mice and give rise to cells with EMT phenotype. Interestingly CD49f+EPCAM+ subpopulation expresses higher ALDH than other two subpopulations with EMT phenotype. Therefore we propose that breast CSCs may exist in two states; EMT state may be represented by CD49f or CD44 and MET state by ALDH expression. Consistent with our hypothesis, ALDH-positive cells compared to ALDH-negative cells within the CD49f+EPCAM+ phenotype have greater capacity to generate CD49f+/EPCAM- phenotype upon IL6 or TGF-b stimulation. Interestingly blocking IL6 and TGF-b in CD49f+/EPCAM- cell population results in MET-CSC phenotype characterized by ALDH expression. It is well known that EMT is characterized by reversible epigenetic changes and therefore we hypothesized that these epigenetic changes might be involved in acquisition of different CSC states.
Our results suggest that interplay between genetic and epigenetic changes during malignant transformation of mammary epithelial cells may activate multiple signaling cascades resulting in expansion of stem cells which display an EMT phenotype. Furthermore, these studies provide a strong rationale for the development of alternative therapeutics which are able to target these different states of cancer stem cells.
Citation Format: Maria Ouzounova, April Davis, Gwangil Kim, Fayaz Malik, Ahmed A. Quraishi, Shawn G. Clouthier, Max S. Wicha, Hasan Korkaya. Epigenetic regulation of cancer stem cell states in a p53/PTEN inactivated mammary epithelial cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5024. doi:10.1158/1538-7445.AM2013-5024
Abstract 5025: Presence of meningioma stroma mesenchymal stem-like cells.
Authors: Kim Eui Hyun , Kang Seok Ku 
Published: August 2014

Abstract
Presence of cells resembling bone marrow-mesenchymal stem cells (BM-MSCs) from glioma was proved, however it has been little known about existence of MSCs from meningioma. We try to investigate whether we are able to isolate cells resembling BM-MSCs. Thus, we hypothesized that cells similar to BM-MSCs exist in meningioma specimen.
We cultured fresh meningioma specimen using the same protocols for culturing BM-MSCs. The cultured cells were analyzed by fluorescence-activated cell sorting (FACS) for surface markers associated with BM-MSCs. These cells were exposed to mesenchymal differentiation conditions. To evaluate the tumorigenecity of cells resembling MSCs from meningioma, we injected these cells into the brain of athymic nude mice. To find possible locations, sections of meningioma specimens were analyzed by immunofluorescent labeling.
In 5 of 17 meningioma specimen, we isolated cells similar to BM-MSCs which were called meningioma stroma mesenchymal stem-like cells (MS-MSCs). MS-MSCs were spindle shaped and adherent cells. FACS analysis showed that the MS-MSCs had similar surface marker to BM-MSCs. (Cells that were positive for two of the markers among CD105, CD90, CD73 and negative for two of the markers among CD45, CD31, NG2 were chosen to see their differentiation capability.) Chosen cells were observed for their ability to differentiate into adipocytes, osteocytes and chondrocytes. MS-MSCs immnohistological analysis indicated that were closely associated with the endothelial cells and pericytes cells. No tumor was discovered within the brains of mice that received the MS-MSCs orthotopic inoculation. Our results recognized that cells similar to BM-MSCs exist in meningioma specimen for the first time. MS-MSCs could be a source of meningioma microenvironment.
Citation Format: Eui Hyun Kim, Seok Ku Kang. Presence of meningioma stroma mesenchymal stem-like cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5025. doi:10.1158/1538-7445.AM2013-5025
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 503: Mammary fibroblasts induce hormone-independent growth in estrogen receptor-positive breast cancer cells via an epithelial-to-mesenchymal transition in a 3D cell culture model.
Authors: Holton Sarah E. , Bergamaschi Anna , Katzenellenbogen Benita S. , Bhargava Rohit 
Published: August 2014

Abstract
The majority of breast cancers diagnosed in the United States are estrogen receptor positive (ER+). These patients may respond to targeted endocrine therapies, but up to 30% of patients experience a cancer recurrence. We hypothesized that the molecular interaction of ER+ breast cancer cells with mammary fibroblasts might lead to endocrine resistance and, eventually, breast cancer relapse. We developed a three-dimensional (3D) co-culture model representing cancer cell-fibroblast interactions during early tumor invasion. We show that the proliferation of MCF7 ER+ cells switches from hormone-dependent to growth factor-dependent in the presence of human mammary fibroblasts. Further, we determine that this transition is associated with gene and protein hallmarks of the epithelial-mesenchymal transition (EMT) in tumor cells, in particular upregulation of SNAIL and SLUG mRNA and loss of E-Cadherin protein. We identified the secreted proteins that arise from epithelial-fibroblast interactions in this system using an antibody-based array. The proteins secreted into the conditioned medium are sufficient to induce EMT markers in primary normal human mammary epithelial cells (HMECs). Our report demonstrates that estrogen receptor activity is dynamic and therefore is not best assessed with immunohistochemical techniques alone. For the facile and rapid determination of ER activity in a clinical setting, we propose the use of an emerging imaging method, highly sensitive label-free Fourier Transform infrared (FT-IR) spectroscopic imaging. We validate this technology in predicting endocrine sensitivity in breast cancer here, by detecting significant changes in spectroscopic peaks correlated with proliferation and metabolism of MCF7 cells grown in 3D culture.
(Supported by grants from The Breast Cancer Research Foundation to BSK, DOD postdoctoral fellowship W81XWH-09-1-0398 to AB, NIH NCI Alliance for Nanotechnology in Cancer ‘Midwest Cancer Nanotechnology Training Center R25 CA154015A to SEH, and National Institutes of Health RO1CA138882 to RB.)
Citation Format: Sarah E. Holton, Anna Bergamaschi, Benita S. Katzenellenbogen, Rohit Bhargava. Mammary fibroblasts induce hormone-independent growth in estrogen receptor-positive breast cancer cells via an epithelial-to-mesenchymal transition in a 3D cell culture model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 503. doi:10.1158/1538-7445.AM2013-503
Abstract 5041: The type III TGF-beta receptor promotes FGF2-mediated neuronal differentiation in neuroblastoma.
Authors: Knelson Erik H. , Gaviglio Angela L. , Tewari Alok K. , Armstrong Michael B. , Nixon Andrew B. , Starr Mark D. , Mythreye Karthikeyan , Blobe Gerard C. 
Published: August 2014

Abstract
Growth factors and their receptors coordinate neuronal differentiation during development, yet their roles in the pediatric tumor neuroblastoma remain unclear. Here we report that expression of type III TGF-beta receptor (TβRIII) mRNA and protein decreases with advancing stage of neuroblastoma and positively correlates with prognosis. TβRIII expression is epigenetically suppressed by MYCN oncogene amplification and TβRIII expression can be used as a prognostic marker in neuroblastoma patients with MYCN amplification. TβRIII expression in neuroblastoma cells promotes neuronal differentiation and enhances the differentiating effects of FGF2 treatment. Mechanistically, glycosaminoglycan modifications on TβRIII bind FGF2 and FGFR1 to promote neuronal differentiation via Erk MAPK and the transcription factor ID1. TβRIII-mediated differentiation suppresses tumor cell proliferation in vitro and in vivo. These studies characterize a novel co-receptor function for TβRIII in FGF2-mediated neuronal differentiation of neuroblastoma cells, while identifying potential therapeutic targets and clinical biomarkers for advanced-stage disease. More generally, our results suggest that the targeting of growth factor receptors and downstream signaling pathways may prove useful in promoting neuronal differentiation to suppress neuroblastoma tumor growth.
Citation Format: Erik H. Knelson, Angela L. Gaviglio, Alok K. Tewari, Michael B. Armstrong, Andrew B. Nixon, Mark D. Starr, Karthikeyan Mythreye, Gerard C. Blobe. The type III TGF-beta receptor promotes FGF2-mediated neuronal differentiation in neuroblastoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5041. doi:10.1158/1538-7445.AM2013-5041
Abstract 505: Hypoxia inducible factor-dependent breast cancer-mesenchymal stem cell bidirectional signaling promotes metastasis.
Authors: Chaturvedi Pallavi , Gilkes Daniele , Semenza Gregg 
Published: August 2014

Abstract
Metastasis involves critical interactions between cancer and stromal cells. Intratumoral hypoxia promotes metastasis through activation of hypoxia-inducible factors (HIFs). We have demonstrated that HIFs mediate paracrine signaling between breast cancer cells (BCCs) and mesenchymal stem cells (MSCs) that facilitate metastasis. In an orthotopic implantation model, MSCs were recruited to primary breast tumors and promoted BCC metastasis to lymph nodes and lungs in a HIF-dependent manner. In vitro gene analysis of co-culture of MSCs with BCCs showed induced expression of the chemokine CXCL10 in MSCs and its cognate receptor CXCR3 in BCCs, which was augmented by hypoxia. Further we showed that CXCR3 expression was blocked in co-cultures treated with neutralizing antibody against CXCL10. Conversely, CXCL10 expression was blocked in MSCs co-cultured with BCCs that did not express CXCR3 or HIFs. MSC co-culture did not enhance the metastasis of CXCR3-deficient or HIF-deficient BCCs. Co-culture of MSCs with BCCs augmented HIF activity in BCCs. BCCs and MSCs expressed placental growth factor (PGF) and its cognate receptor VEGF1, respectively, in a HIF-dependent manner. The expression of CXCL10 by MSCs was dependent on PGF expression by BCCs. PGF promoted metastasis of BCCs and also facilitated homing of MSCs to tumors. Thus, HIFs mediate complex and bidirectional paracrine signaling between BCCs and MSCs that stimulates breast cancer metastasis.
Citation Format: Pallavi Chaturvedi, Daniele Gilkes, Gregg Semenza. Hypoxia inducible factor-dependent breast cancer-mesenchymal stem cell bidirectional signaling promotes metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 505. doi:10.1158/1538-7445.AM2013-505