3D hydrogel breast cancer models for studying the effects of hypoxia on epithelial to mesenchymal transition

Ying Wang, Sameer Mirza, Shaohua Wu, Jiping Zeng, Wen Shi, Hamid Band, Vimla Band, Bin Duan

Research output: Contribution to journalArticle

Abstract

Solid tumors are 3D assemblies of cancer cells, together with multiple stromal cell types within an extracellular matrix. Yet, the vast majority of cell-based studies to characterize oncogenesis and discovery of new anti-cancer drugs is conducted using conventional 2D monolayer culture systems, where cells are grown on plastic substratum under normoxic environments. In current study, we generated 3D breast cancer cell culture platform consists of photocrosslinkable hydrogels and encapsulated isogenic primary (21PT) and a metastatic (21MT-2) breast cancer cell lines derived from the primary tumor and pleural effusion from the same patient. We demonstrated that hypoxia decreased cellular assembly size and density, and promoted epithelial to mesenchymal transition (EMT) process, without affecting cell viability. Next, we showed hypoxia enhanced breast cancer cell migration, and expression and secretion of lysyl oxidase (LOX), which is copper-dependent amine oxidase and has the primary function to drive the crosslinking of collagen and elastin and is regulated by hypoxia. Furthermore, to recapitulate in vivo situation, we generated breast cancer and lung cells (derived from the same patient) contact model by stacking 3D hydrogel constructs with breast cancer cells onto lung mesenchymal cells (LMC) laden-hydrogel and then showed breast cancer cells migrated towards LMC during hypoxia. Lastly, as a validation of this model for future screen of therapeutic agents, we demonstrated that LOX inhibitor exhibited a significant decrease in breast cancer cell viability, migration, and EMT. Taken together, these results validate the use of hydrogels based models to examine hypoxia related EMT in breast cancer cells.

LanguageEnglish (US)
Pages32191-32203
Number of pages13
JournalOncotarget
Volume9
Issue number63
DOIs
StatePublished - Aug 14 2018

Fingerprint

Epithelial-Mesenchymal Transition
Hydrogel
Breast Neoplasms
Protein-Lysine 6-Oxidase
Cell Hypoxia
Hydrogels
Cell Movement
Neoplasms
Cell Survival
Cell Culture Techniques
Amine Oxidase (Copper-Containing)
Lung
Hypoxia
Elastin
Pleural Effusion
Stromal Cells
Plastics
Extracellular Matrix
Lung Neoplasms
Carcinogenesis

Keywords

  • Epithelial-mesenchymal transition
  • Hydrogel
  • Hypoxia
  • Lysyl oxidase

ASJC Scopus subject areas

  • Oncology

Cite this

3D hydrogel breast cancer models for studying the effects of hypoxia on epithelial to mesenchymal transition. / Wang, Ying; Mirza, Sameer; Wu, Shaohua; Zeng, Jiping; Shi, Wen; Band, Hamid; Band, Vimla; Duan, Bin.

In: Oncotarget, Vol. 9, No. 63, 14.08.2018, p. 32191-32203.

Research output: Contribution to journalArticle

Wang, Ying ; Mirza, Sameer ; Wu, Shaohua ; Zeng, Jiping ; Shi, Wen ; Band, Hamid ; Band, Vimla ; Duan, Bin. / 3D hydrogel breast cancer models for studying the effects of hypoxia on epithelial to mesenchymal transition. In: Oncotarget. 2018 ; Vol. 9, No. 63. pp. 32191-32203.
@article{e34fd3066d214999a23131913ae4a5e3,
title = "3D hydrogel breast cancer models for studying the effects of hypoxia on epithelial to mesenchymal transition",
abstract = "Solid tumors are 3D assemblies of cancer cells, together with multiple stromal cell types within an extracellular matrix. Yet, the vast majority of cell-based studies to characterize oncogenesis and discovery of new anti-cancer drugs is conducted using conventional 2D monolayer culture systems, where cells are grown on plastic substratum under normoxic environments. In current study, we generated 3D breast cancer cell culture platform consists of photocrosslinkable hydrogels and encapsulated isogenic primary (21PT) and a metastatic (21MT-2) breast cancer cell lines derived from the primary tumor and pleural effusion from the same patient. We demonstrated that hypoxia decreased cellular assembly size and density, and promoted epithelial to mesenchymal transition (EMT) process, without affecting cell viability. Next, we showed hypoxia enhanced breast cancer cell migration, and expression and secretion of lysyl oxidase (LOX), which is copper-dependent amine oxidase and has the primary function to drive the crosslinking of collagen and elastin and is regulated by hypoxia. Furthermore, to recapitulate in vivo situation, we generated breast cancer and lung cells (derived from the same patient) contact model by stacking 3D hydrogel constructs with breast cancer cells onto lung mesenchymal cells (LMC) laden-hydrogel and then showed breast cancer cells migrated towards LMC during hypoxia. Lastly, as a validation of this model for future screen of therapeutic agents, we demonstrated that LOX inhibitor exhibited a significant decrease in breast cancer cell viability, migration, and EMT. Taken together, these results validate the use of hydrogels based models to examine hypoxia related EMT in breast cancer cells.",
keywords = "Epithelial-mesenchymal transition, Hydrogel, Hypoxia, Lysyl oxidase",
author = "Ying Wang and Sameer Mirza and Shaohua Wu and Jiping Zeng and Wen Shi and Hamid Band and Vimla Band and Bin Duan",
year = "2018",
month = "8",
day = "14",
doi = "10.18632/oncotarget.25891",
language = "English (US)",
volume = "9",
pages = "32191--32203",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "63",

}

TY - JOUR

T1 - 3D hydrogel breast cancer models for studying the effects of hypoxia on epithelial to mesenchymal transition

AU - Wang, Ying

AU - Mirza, Sameer

AU - Wu, Shaohua

AU - Zeng, Jiping

AU - Shi, Wen

AU - Band, Hamid

AU - Band, Vimla

AU - Duan, Bin

PY - 2018/8/14

Y1 - 2018/8/14

N2 - Solid tumors are 3D assemblies of cancer cells, together with multiple stromal cell types within an extracellular matrix. Yet, the vast majority of cell-based studies to characterize oncogenesis and discovery of new anti-cancer drugs is conducted using conventional 2D monolayer culture systems, where cells are grown on plastic substratum under normoxic environments. In current study, we generated 3D breast cancer cell culture platform consists of photocrosslinkable hydrogels and encapsulated isogenic primary (21PT) and a metastatic (21MT-2) breast cancer cell lines derived from the primary tumor and pleural effusion from the same patient. We demonstrated that hypoxia decreased cellular assembly size and density, and promoted epithelial to mesenchymal transition (EMT) process, without affecting cell viability. Next, we showed hypoxia enhanced breast cancer cell migration, and expression and secretion of lysyl oxidase (LOX), which is copper-dependent amine oxidase and has the primary function to drive the crosslinking of collagen and elastin and is regulated by hypoxia. Furthermore, to recapitulate in vivo situation, we generated breast cancer and lung cells (derived from the same patient) contact model by stacking 3D hydrogel constructs with breast cancer cells onto lung mesenchymal cells (LMC) laden-hydrogel and then showed breast cancer cells migrated towards LMC during hypoxia. Lastly, as a validation of this model for future screen of therapeutic agents, we demonstrated that LOX inhibitor exhibited a significant decrease in breast cancer cell viability, migration, and EMT. Taken together, these results validate the use of hydrogels based models to examine hypoxia related EMT in breast cancer cells.

AB - Solid tumors are 3D assemblies of cancer cells, together with multiple stromal cell types within an extracellular matrix. Yet, the vast majority of cell-based studies to characterize oncogenesis and discovery of new anti-cancer drugs is conducted using conventional 2D monolayer culture systems, where cells are grown on plastic substratum under normoxic environments. In current study, we generated 3D breast cancer cell culture platform consists of photocrosslinkable hydrogels and encapsulated isogenic primary (21PT) and a metastatic (21MT-2) breast cancer cell lines derived from the primary tumor and pleural effusion from the same patient. We demonstrated that hypoxia decreased cellular assembly size and density, and promoted epithelial to mesenchymal transition (EMT) process, without affecting cell viability. Next, we showed hypoxia enhanced breast cancer cell migration, and expression and secretion of lysyl oxidase (LOX), which is copper-dependent amine oxidase and has the primary function to drive the crosslinking of collagen and elastin and is regulated by hypoxia. Furthermore, to recapitulate in vivo situation, we generated breast cancer and lung cells (derived from the same patient) contact model by stacking 3D hydrogel constructs with breast cancer cells onto lung mesenchymal cells (LMC) laden-hydrogel and then showed breast cancer cells migrated towards LMC during hypoxia. Lastly, as a validation of this model for future screen of therapeutic agents, we demonstrated that LOX inhibitor exhibited a significant decrease in breast cancer cell viability, migration, and EMT. Taken together, these results validate the use of hydrogels based models to examine hypoxia related EMT in breast cancer cells.

KW - Epithelial-mesenchymal transition

KW - Hydrogel

KW - Hypoxia

KW - Lysyl oxidase

UR - http://www.scopus.com/inward/record.url?scp=85051601691&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85051601691&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.25891

DO - 10.18632/oncotarget.25891

M3 - Article

VL - 9

SP - 32191

EP - 32203

JO - Oncotarget

T2 - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 63

ER -