Abstract A71: Her-4 mediates anoikis resistance, chemoresistance, and metastatic potential in osteosarcoma

作者：Rocío K. Rivera-Valentín, Yingqi Hua, Yi Zhang, Nupur Lala, Yanwen Yang, Dennis P.M. Hughes · 发表于：Cancer Research · 年份：2014 · DOI：10.1158/1538-7445.pedcan-a71 · 被引用次数：2 · 研究领域：Neuroblastoma Research and Treatments、Cancer, Hypoxia, and Metabolism、Lung Cancer Research Studies

Abstract Osteosarcoma (OS) is the most common primary bone cancer in children, and despite more than 20 years of clinical trials, the 5-year survival for OS patients remains essentially unchanged (∼70% for non-metastatic patients and 30% for metastatic patients), with the vast majority deaths arising from metastasis to lungs or bones. We wanted to identify signaling pathways that mediate tumor survival and metastasis in OS, and we focused on Her-4 (ERBB4), which promoted survival on neuroblastoma cells in our previous work. Purpose: To evaluate the role of Her-4 in OS cell survival, metastasis and “stemness”. Methods: Her-4 expression was measured by flow cytometry, western blot and Q-PCR. Validated OS cell lines were manipulated with shRNA to knock-down Her-4 (compared to scrambled control). In vitro responses were measured by varying culture conditions (normal, high-density or anchorage-independent growth), serum starvation, hypoxia or chemotherapy (methotrexate, cisplatin, doxorubicin and 4-OH-ifosfamide) and measuring proliferation, cell cycle, and apoptosis (by both flow cytometry and PARP cleavage). A sarcosphere assay assessed expression of “stemness” markers, or tumor initiating cells (TICs), and Her-4 expression. The luciferase-labeled CCH-OS-O xenograft model was used to assess the impact of Her-4 knock-down on metastatic potential, with weekly luciferase measures (IVIS 100, Xenogen) assessing tumor burden. Immunohistochemistry (IHC) assessed Her-4 expression in arc...