TY - JOUR
T1 - A Spontaneous 3D Bone-On-a-Chip for Bone Metastasis Study of Breast Cancer Cells
AU - Hao, Sijie
AU - Ha, Laura
AU - Cheng, Gong
AU - Wan, Yuan
AU - Xia, Yiqiu
AU - Sosnoski, Donna M.
AU - Mastro, Andrea M.
AU - Zheng, Si Yang
N1 - Funding Information:
The authors appreciate assistance and help from Dr. Gang Ning, Director of the Penn State Microscopy & Cytometry Facility, for TEM imaging. The authors appreciate the kind donation of CNA35 from Dr. Magnus Hook, Texas A&M University. The authors thank Brian McKellar, Penn State, for printing 3D molds. This work was supported by the American Cancer Society under grant number RSG-13-009-01-CDD to S.-Y.Z. and a Pennsylvania Breast Cancer Coalition research grant to S.-Y.Z. and A.M.M.
Publisher Copyright:
© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2018/3/22
Y1 - 2018/3/22
N2 - Bone metastasis occurs at ≈70% frequency in metastatic breast cancer. The mechanisms used by tumors to hijack the skeleton, promote bone metastases, and confer therapeutic resistance are poorly understood. This has led to the development of various bone models to investigate the interactions between cancer cells and host bone marrow cells and related physiological changes. However, it is challenging to perform bone studies due to the difficulty in periodic sampling. Herein, a bone-on-a-chip (BC) is reported for spontaneous growth of a 3D, mineralized, collagenous bone tissue. Mature osteoblastic tissue of up to 85 µm thickness containing heavily mineralized collagen fibers naturally formed in 720 h without the aid of differentiation agents. Moreover, co-culture of metastatic breast cancer cells is examined with osteoblastic tissues. The new bone-on-a-chip design not only increases experimental throughput by miniaturization, but also maximizes the chances of cancer cell interaction with bone matrix of a concentrated surface area and facilitates easy, frequent observation. As a result, unique hallmarks of breast cancer bone colonization, previously confirmed only in vivo, are observed. The spontaneous 3D BC keeps the promise as a physiologically relevant model for the in vitro study of breast cancer bone metastasis.
AB - Bone metastasis occurs at ≈70% frequency in metastatic breast cancer. The mechanisms used by tumors to hijack the skeleton, promote bone metastases, and confer therapeutic resistance are poorly understood. This has led to the development of various bone models to investigate the interactions between cancer cells and host bone marrow cells and related physiological changes. However, it is challenging to perform bone studies due to the difficulty in periodic sampling. Herein, a bone-on-a-chip (BC) is reported for spontaneous growth of a 3D, mineralized, collagenous bone tissue. Mature osteoblastic tissue of up to 85 µm thickness containing heavily mineralized collagen fibers naturally formed in 720 h without the aid of differentiation agents. Moreover, co-culture of metastatic breast cancer cells is examined with osteoblastic tissues. The new bone-on-a-chip design not only increases experimental throughput by miniaturization, but also maximizes the chances of cancer cell interaction with bone matrix of a concentrated surface area and facilitates easy, frequent observation. As a result, unique hallmarks of breast cancer bone colonization, previously confirmed only in vivo, are observed. The spontaneous 3D BC keeps the promise as a physiologically relevant model for the in vitro study of breast cancer bone metastasis.
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U2 - 10.1002/smll.201702787
DO - 10.1002/smll.201702787
M3 - Article
C2 - 29399951
AN - SCOPUS:85041628066
SN - 1613-6810
VL - 14
JO - Small
JF - Small
IS - 12
M1 - 1702787
ER -
