A Spontaneous 3D Bone-On-a-Chip for Bone Metastasis Study of Breast Cancer Cells

Sijie Hao, Laura Ha, Gong Cheng, Yuan Wan, Yiqiu Xia, Donna M. Sosnoski, Andrea M. Mastro, Siyang Zheng

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number1702787
JournalSmall
Volume14
Issue number12
DOIs
StatePublished - Mar 22 2018

Fingerprint

Bone
Cells
Breast Neoplasms
Neoplasm Metastasis
Bone and Bones
Bone Neoplasms
Miniaturization
Neoplasms
Tissue
Bone Matrix
Bone Development
Coculture Techniques
Skeleton
Cell Communication
Bone Marrow Cells
Collagen
Observation
Cell culture
Growth
Tumors

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biomaterials
  • Chemistry(all)
  • Materials Science(all)
  • Engineering (miscellaneous)

Cite this

Hao, S., Ha, L., Cheng, G., Wan, Y., Xia, Y., Sosnoski, D. M., ... Zheng, S. (2018). A Spontaneous 3D Bone-On-a-Chip for Bone Metastasis Study of Breast Cancer Cells. Small, 14(12), [1702787]. https://doi.org/10.1002/smll.201702787
Hao, Sijie ; Ha, Laura ; Cheng, Gong ; Wan, Yuan ; Xia, Yiqiu ; Sosnoski, Donna M. ; Mastro, Andrea M. ; Zheng, Siyang. / A Spontaneous 3D Bone-On-a-Chip for Bone Metastasis Study of Breast Cancer Cells. In: Small. 2018 ; Vol. 14, No. 12.
@article{b5610c4e3ebd4a98859a0cc13e99ad33,
title = "A Spontaneous 3D Bone-On-a-Chip for Bone Metastasis Study of Breast Cancer Cells",
abstract = "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.",
author = "Sijie Hao and Laura Ha and Gong Cheng and Yuan Wan and Yiqiu Xia and Sosnoski, {Donna M.} and Mastro, {Andrea M.} and Siyang Zheng",
year = "2018",
month = "3",
day = "22",
doi = "10.1002/smll.201702787",
language = "English (US)",
volume = "14",
journal = "Small",
issn = "1613-6810",
publisher = "Wiley-VCH Verlag",
number = "12",

}

Hao, S, Ha, L, Cheng, G, Wan, Y, Xia, Y, Sosnoski, DM, Mastro, AM & Zheng, S 2018, 'A Spontaneous 3D Bone-On-a-Chip for Bone Metastasis Study of Breast Cancer Cells', Small, vol. 14, no. 12, 1702787. https://doi.org/10.1002/smll.201702787

A Spontaneous 3D Bone-On-a-Chip for Bone Metastasis Study of Breast Cancer Cells. / Hao, Sijie; Ha, Laura; Cheng, Gong; Wan, Yuan; Xia, Yiqiu; Sosnoski, Donna M.; Mastro, Andrea M.; Zheng, Siyang.

In: Small, Vol. 14, No. 12, 1702787, 22.03.2018.

Research output: Contribution to journalArticle

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, Siyang

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.

UR - http://www.scopus.com/inward/record.url?scp=85041628066&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041628066&partnerID=8YFLogxK

U2 - 10.1002/smll.201702787

DO - 10.1002/smll.201702787

M3 - Article

C2 - 29399951

AN - SCOPUS:85041628066

VL - 14

JO - Small

JF - Small

SN - 1613-6810

IS - 12

M1 - 1702787

ER -

Hao S, Ha L, Cheng G, Wan Y, Xia Y, Sosnoski DM et al. A Spontaneous 3D Bone-On-a-Chip for Bone Metastasis Study of Breast Cancer Cells. Small. 2018 Mar 22;14(12). 1702787. https://doi.org/10.1002/smll.201702787