原创力文档a novel 3-d mineralized tumor model to study breast cancer bone metastasis一种新型三维矿化肿瘤模型研究乳腺癌骨转移.pdfVIP
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a novel 3-d mineralized tumor model to study breast cancer bone metastasis一种新型三维矿化肿瘤模型研究乳腺癌骨转移
A Novel 3-D Mineralized Tumor Model to Study Breast
Cancer Bone Metastasis
Siddharth P. Pathi, Christine Kowalczewski, Ramya Tadipatri, Claudia Fischbach*
Department of Biomedical Engineering, Cornell University, Ithaca, New York, United States of America
Abstract
Background: Metastatic bone disease is a frequent cause of morbidity in patients with advanced breast cancer, but the role
of the bone mineral hydroxyapatite (HA) in this process remains unclear. We have developed a novel mineralized 3-D tumor
model and have employed this culture system to systematically investigate the pro-metastatic role of HA under
physiologically relevant conditions in vitro.
Methodology/Principal Findings: MDA-MB231 breast cancer cells were cultured within non-mineralized or mineralized
polymeric scaffolds fabricated by a gas foaming-particulate leaching technique. Tumor cell adhesion, proliferation, and
secretion of pro-osteoclastic interleukin-8 (IL-8) was increased in mineralized tumor models as compared to non-mineralized
tumor models, and IL-8 secretion was more pronounced for bone-specific MDA-MB231 subpopulations relative to lung-
specific breast cancer cells. These differences were pathologically significant as conditioned media collected from
mineralized tumor models promoted osteoclastogenesis in an IL-8 dependent manner. Finally, drug testing and signaling
studies with transforming growth factor beta (TGFb) confirmed the clinical relevance of our culture system and revealed
that breast cancer cell behavior is broadly affected by HA.
Conclusions/Significance: Our results indicate that HA promotes features associated with the neoplastic and metastatic
growth of breast carcinoma cells in bone and that IL-8 may play an important role in this proces
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