Search Results
Search for other papers by Gina Chia-Yi Chu in
Google Scholar
PubMed
Search for other papers by Haiyen E Zhau in
Google Scholar
PubMed
Search for other papers by Ruoxiang Wang in
Google Scholar
PubMed
Uro-Oncology Research, Surgery, Biomedical Sciences, Biostatistics and Bioinformatics Center, Department of Pathology, Department of Pathology, Department of Biochemistry and Cell Biology, Department of Medicine, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8750 Beverly Blvd., Atrium 103, Los Angeles, California 90048, USA Departments of
Search for other papers by André Rogatko in
Google Scholar
PubMed
Search for other papers by Xu Feng in
Google Scholar
PubMed
Search for other papers by Majd Zayzafoon in
Google Scholar
PubMed
Search for other papers by Youhua Liu in
Google Scholar
PubMed
Search for other papers by Mary C Farach-Carson in
Google Scholar
PubMed
Uro-Oncology Research, Surgery, Biomedical Sciences, Biostatistics and Bioinformatics Center, Department of Pathology, Department of Pathology, Department of Biochemistry and Cell Biology, Department of Medicine, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8750 Beverly Blvd., Atrium 103, Los Angeles, California 90048, USA Departments of
Search for other papers by Sungyong You in
Google Scholar
PubMed
Uro-Oncology Research, Surgery, Biomedical Sciences, Biostatistics and Bioinformatics Center, Department of Pathology, Department of Pathology, Department of Biochemistry and Cell Biology, Department of Medicine, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8750 Beverly Blvd., Atrium 103, Los Angeles, California 90048, USA Departments of
Search for other papers by Jayoung Kim in
Google Scholar
PubMed
Uro-Oncology Research, Surgery, Biomedical Sciences, Biostatistics and Bioinformatics Center, Department of Pathology, Department of Pathology, Department of Biochemistry and Cell Biology, Department of Medicine, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8750 Beverly Blvd., Atrium 103, Los Angeles, California 90048, USA Departments of
Uro-Oncology Research, Surgery, Biomedical Sciences, Biostatistics and Bioinformatics Center, Department of Pathology, Department of Pathology, Department of Biochemistry and Cell Biology, Department of Medicine, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8750 Beverly Blvd., Atrium 103, Los Angeles, California 90048, USA Departments of
Search for other papers by Michael R Freeman in
Google Scholar
PubMed
Uro-Oncology Research, Surgery, Biomedical Sciences, Biostatistics and Bioinformatics Center, Department of Pathology, Department of Pathology, Department of Biochemistry and Cell Biology, Department of Medicine, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, 8750 Beverly Blvd., Atrium 103, Los Angeles, California 90048, USA Departments of
Search for other papers by Leland W K Chung in
Google Scholar
PubMed
Prostate cancer (PCa) metastasis to bone is lethal and there is no adequate animal model for studying the mechanisms underlying the metastatic process. Here, we report that receptor activator of NF-κB ligand (RANKL) expressed by PCa cells consistently induced colonization or metastasis to bone in animal models. RANK-mediated signaling established a premetastatic niche through a feed-forward loop, involving the induction of RANKL and c-Met, but repression of androgen receptor (AR) expression and AR signaling pathways. Site-directed mutagenesis and transcription factor (TF) deletion/interference assays identified common TF complexes, c-Myc/Max, and AP4 as critical regulatory nodes. RANKL–RANK signaling activated a number of master regulator TFs that control the epithelial-to-mesenchymal transition (Twist1, Slug, Zeb1, and Zeb2), stem cell properties (Sox2, Myc, Oct3/4, and Nanog), neuroendocrine differentiation (Sox9, HIF1α, and FoxA2), and osteomimicry (c-Myc/Max, Sox2, Sox9, HIF1α, and Runx2). Abrogating RANK or its downstream c-Myc/Max or c-Met signaling network minimized or abolished skeletal metastasis in mice. RANKL-expressing LNCaP cells recruited and induced neighboring non metastatic LNCaP cells to express RANKL, c-Met/activated c-Met, while downregulating AR expression. These initially non-metastatic cells, once retrieved from the tumors, acquired the potential to colonize and grow in bone. These findings identify a novel mechanism of tumor growth in bone that involves tumor cell reprogramming via RANK–RANKL signaling, as well as a form of signal amplification that mediates recruitment and stable transformation of non-metastatic bystander dormant cells.
Search for other papers by Cassia Michael in
Google Scholar
PubMed
Search for other papers by Juliana Moreira Mendonça-Gomes in
Google Scholar
PubMed
Search for other papers by Clinton Walton DePaolo in
Google Scholar
PubMed
Department of Medicine (Oncology), Albert Einstein College of Medicine, Bronx, New York, USA
Montefiore-Einstein Comprehensive Cancer Research Center, Albert Einstein College of Medicine, Bronx, New York, USA
Cancer Dormancy Tumor Microenvironment Institute, Albert Einstein College of Medicine, Bronx, New York, USA
Search for other papers by Antonio Di Cristofano in
Google Scholar
PubMed
Montefiore-Einstein Comprehensive Cancer Research Center, Albert Einstein College of Medicine, Bronx, New York, USA
Cancer Dormancy Tumor Microenvironment Institute, Albert Einstein College of Medicine, Bronx, New York, USA
Department of Medicine (Hepatology), Albert Einstein College of Medicine, Bronx, New York, USA
Marion Bessin Liver Research Center, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, USA
Search for other papers by Sofia de Oliveira in
Google Scholar
PubMed
Anaplastic thyroid cancer (ATC) is of the most aggressive thyroid cancer. While ATC is rare, it accounts for a disproportionately high number of thyroid cancer-related deaths. Here, we developed an ATC xenotransplant model in zebrafish larvae, where we can study tumorigenesis and therapeutic response in vivo. Using both mouse (T4888M) and human (C643)-derived fluorescently labeled ATC cell lines, we show these cell lines display different engraftment rates, mass volume, proliferation, cell death, angiogenic potential, and neutrophil and macrophage recruitment and infiltration. Next, using a PIP-FUCCI reporter to track proliferation in vivo, we observed cells in each phase of the cell cycle. Additionally, we performed long-term non-invasive intravital microscopy over 48 h to understand cellular dynamics in the tumor microenvironment at the single-cell level. Lastly, we tested two drug treatments, AZD2014 and a combination therapy of dabrafenib and trametinib, to show our model could be used as an effective screening platform for new therapeutic compounds for ATC. Altogether, we show that zebrafish xenotransplants make a great model to study thyroid carcinogenesis and the tumor microenvironment, while also being a suitable model to test new therapeutics in vivo.
Search for other papers by John E Phay in
Google Scholar
PubMed
Search for other papers by Matthew D Ringel in
Google Scholar
PubMed
supporting cancer dormancy using thyroid cancer as an example ( Folkman & Kalluri 2004 ). Because of their rapid proliferation and abnormal vasculature, aggressive solid tumors possess regions where nutrients and oxygen are limiting. Oxygen availability is
Search for other papers by Penelope D Ottewell in
Google Scholar
PubMed
Search for other papers by Ning Wang in
Google Scholar
PubMed
Search for other papers by Joshua Meek in
Google Scholar
PubMed
Search for other papers by C Anne Fowles in
Google Scholar
PubMed
Search for other papers by Peter I Croucher in
Google Scholar
PubMed
Search for other papers by Colby L Eaton in
Google Scholar
PubMed
Search for other papers by Ingunn Holen in
Google Scholar
PubMed
for cancer dormancy . Nature Reviews. Cancer 7 834 – 846 . ( doi:10.1038/nrc2256 ). American Cancer Society 2013 Survival rates for prostate cancer. Atlanta, GA, USA: American Cancer Society. (available at: http
Search for other papers by Marc Lacroix in
Google Scholar
PubMed
Clinical Pathology 59 289 –297. Aguirre-Ghiso JA 2006 The problem of cancer dormancy: understanding the basic mechanisms and identifying therapeutic opportunities. Cell Cycle 5 1740 –1743
Search for other papers by Ralph Blumhardt in
Google Scholar
PubMed
University of Texas Health Science Center at San Antonio, San Antonio Military Medical Center, Tennessee Valley VA Healthcare System, Vanderbilt University Medical Center, UAMS Thyroid Center, San Antonio, Texas, USA
Search for other papers by Ely A Wolin in
Google Scholar
PubMed
Search for other papers by William T Phillips in
Google Scholar
PubMed
Search for other papers by Umber A Salman in
Google Scholar
PubMed
University of Texas Health Science Center at San Antonio, San Antonio Military Medical Center, Tennessee Valley VA Healthcare System, Vanderbilt University Medical Center, UAMS Thyroid Center, San Antonio, Texas, USA
Search for other papers by Ronald C Walker in
Google Scholar
PubMed
Search for other papers by Brendan C Stack Jr in
Google Scholar
PubMed
Search for other papers by Darlene Metter in
Google Scholar
PubMed
Windsor J Thrush G Scheuermann RH Uhr JW Street NE 1999 Cancer dormancy. VII. A regulatory role for CD8+ T cells and IFN-γ in establishing and maintaining the tumor-dormant state . Journal of Immunology 162
Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea
Search for other papers by Hyun Ho Han in
Google Scholar
PubMed
Search for other papers by Baek Gil Kim in
Google Scholar
PubMed
Search for other papers by Joo Hyun Lee in
Google Scholar
PubMed
Search for other papers by Suki Kang in
Google Scholar
PubMed
Search for other papers by Ji Eun Kim in
Google Scholar
PubMed
Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea
Severance Biomedical Science Institute (SBSI), Yonsei University College of Medicine, Seoul, South Korea
Global 5-5-10 System Biology, Yonsei University, Seoul, South Korea
Search for other papers by Nam Hoon Cho in
Google Scholar
PubMed
contributed to experimental conception, data interpretation and manuscript revision. References Aguirre-Ghiso JA 2007 Models, mechanisms and clinical evidence for cancer dormancy . Nature Reviews Cancer 7 834 – 846 . ( doi:10.1038/nrc2256
Search for other papers by Claudia Tulotta in
Google Scholar
PubMed
Search for other papers by Penelope Ottewell in
Google Scholar
PubMed
signalling in breast cancer dormancy in bone. IL-1B has been shown to have profound effects on tumour growth and metastasis in tumour types other than breast cancer, including melanoma. A reduction of local tumours or lung metastasis was found in
