title: A microengineered pathophysiological model of early-stage breast cancer.
abstract: A mounting body of evidence in cancer research suggests that the local microenvironment of tumor cells has a profound influence on cancer progression and metastasis. In vitro studies on the tumor microenvironment and its pharmacological modulation, however, are often hampered by the technical challenges associated with creating physiological cell culture environments that integrate cancer cells with the key components of their native niche such as neighboring cells and extracellular matrix (ECM) to mimic complex microarchitecture of cancerous tissue. Using early-stage breast cancer as a model disease, here we describe a biomimetic microengineering strategy to reconstitute three-dimensional (3D) structural organization and microenvironment of breast tumors in human cell-based in vitro models. Specifically, we developed a microsystem that enabled co-culture of breast tumor spheroids with human mammary ductal epithelial cells and mammary fibroblasts in a compartmentalized 3D microfluidic device to replicate microarchitecture of breast ductal carcinoma in situ (DCIS). We also explored the potential of this breast cancer-on-a-chip system as a drug screening platform by evaluating the efficacy and toxicity of an anticancer drug (paclitaxel). Our microengineered disease model represents the first critical step towards recapitulating pathophysiological complexity of breast cancer, and may serve as an enabling tool to systematically examine the contribution of the breast cancer microenvironment to the progression of DCIS to an invasive form of the disease.
authors.affiliation: Department of Radiology, Seoul National University Hospital, Seoul, 110-744, Republic of Korea. moonwk@snu.ac.kr.
authors.forename: Yoonseok
authors.initials: Y
authors.lastname: Choi
authors.forename: Eunjeh
authors.initials: E
authors.lastname: Hyun
authors.forename: Jeongyun
authors.initials: J
authors.lastname: Seo
authors.forename: Cassidy
authors.initials: C
authors.lastname: Blundell
authors.forename: Hee Chan
authors.initials: HC
authors.lastname: Kim
authors.forename: Eunhee
authors.initials: E
authors.lastname: Lee
authors.forename: Su Hyun
authors.initials: SH
authors.lastname: Lee
authors.forename: Aree
authors.initials: A
authors.lastname: Moon
authors.forename: Woo Kyung
authors.initials: WK
authors.lastname: Moon
authors.forename: Dongeun
authors.initials: D
authors.lastname: Huh
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity; D001943:Breast Neoplasms / Q000503:physiopathology*; D002277:Carcinoma / Q000503:physiopathology*; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods*; D008954:Models, Biological; D017239:Paclitaxel / Q000633:toxicity; D059016:Tumor Microenvironment
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel