Chitosan-based thermoreversible hydrogel as an in Vitro tumor microenvironment for testing breast cancer therapies

Ching Ting Tsao, Forrest M Kievit, Kui Wang, Ariane E. Erickson, Richard G. Ellenbogen, Miqin Zhang

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Breast cancer is a major health problem for women worldwide. Although in vitro culture of established breast cancer cell lines is the most widely used model for preclinical assessment, it poorly represents the behavior of breast cancers in vivo. Acceleration of the development of effective therapeutic strategies requires a cost-efficient in vitro model that can more accurately resemble the in vivo tumor microenvironment. Here, we report the use of a thermoreversible poly(ethylene glycol)-g-chitosan hydrogel (PCgel) as an in vitro breast cancer model. We hypothesized that PCgel could provide a tumor microenvironment that promotes cultured cancer cells to a more malignant phenotype with drug and immune resistance. Traditional tissue culture plates and Matrigel were applied as controls in our studies. In vitro cellular proliferation and morphology, the secretion of angiogenesis-related growth factors and cytokines, and drug and immune resistance were assessed. Our results show that PCgel cultures promoted tumor aggregate formation, increased secretion of various angiogenesis- and metastasis-related growth factors and cytokines, and increased tumor cell resistance to chemotherapeutic drugs and immunotherapeutic T cells. This PCgel platform may offer a valuable strategy to bridge the gap between standard in vitro and costly animal studies for a wide variety of experimental designs.

Original languageEnglish (US)
Pages (from-to)2134-2142
Number of pages9
JournalMolecular Pharmaceutics
Volume11
Issue number7
DOIs
StatePublished - Jul 7 2014

Fingerprint

Tumor Microenvironment
Hydrogel
Chitosan
Breast Neoplasms
Drug Resistance
Intercellular Signaling Peptides and Proteins
Cytokines
Therapeutics
Neoplasms
Women's Health
Cultured Cells
Research Design
Cell Proliferation
In Vitro Techniques
Neoplasm Metastasis
T-Lymphocytes
Phenotype
Costs and Cost Analysis
Cell Line
Pharmaceutical Preparations

Keywords

  • breast cancer
  • chitosan
  • hydrogel
  • malignancy
  • microenvironment

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Chitosan-based thermoreversible hydrogel as an in Vitro tumor microenvironment for testing breast cancer therapies. / Tsao, Ching Ting; Kievit, Forrest M; Wang, Kui; Erickson, Ariane E.; Ellenbogen, Richard G.; Zhang, Miqin.

In: Molecular Pharmaceutics, Vol. 11, No. 7, 07.07.2014, p. 2134-2142.

Research output: Contribution to journalArticle

Tsao, Ching Ting ; Kievit, Forrest M ; Wang, Kui ; Erickson, Ariane E. ; Ellenbogen, Richard G. ; Zhang, Miqin. / Chitosan-based thermoreversible hydrogel as an in Vitro tumor microenvironment for testing breast cancer therapies. In: Molecular Pharmaceutics. 2014 ; Vol. 11, No. 7. pp. 2134-2142.
@article{7a4886902f404968826a6b9e83e3c32b,
title = "Chitosan-based thermoreversible hydrogel as an in Vitro tumor microenvironment for testing breast cancer therapies",
abstract = "Breast cancer is a major health problem for women worldwide. Although in vitro culture of established breast cancer cell lines is the most widely used model for preclinical assessment, it poorly represents the behavior of breast cancers in vivo. Acceleration of the development of effective therapeutic strategies requires a cost-efficient in vitro model that can more accurately resemble the in vivo tumor microenvironment. Here, we report the use of a thermoreversible poly(ethylene glycol)-g-chitosan hydrogel (PCgel) as an in vitro breast cancer model. We hypothesized that PCgel could provide a tumor microenvironment that promotes cultured cancer cells to a more malignant phenotype with drug and immune resistance. Traditional tissue culture plates and Matrigel were applied as controls in our studies. In vitro cellular proliferation and morphology, the secretion of angiogenesis-related growth factors and cytokines, and drug and immune resistance were assessed. Our results show that PCgel cultures promoted tumor aggregate formation, increased secretion of various angiogenesis- and metastasis-related growth factors and cytokines, and increased tumor cell resistance to chemotherapeutic drugs and immunotherapeutic T cells. This PCgel platform may offer a valuable strategy to bridge the gap between standard in vitro and costly animal studies for a wide variety of experimental designs.",
keywords = "breast cancer, chitosan, hydrogel, malignancy, microenvironment",
author = "Tsao, {Ching Ting} and Kievit, {Forrest M} and Kui Wang and Erickson, {Ariane E.} and Ellenbogen, {Richard G.} and Miqin Zhang",
year = "2014",
month = "7",
day = "7",
doi = "10.1021/mp5002119",
language = "English (US)",
volume = "11",
pages = "2134--2142",
journal = "Molecular Pharmaceutics",
issn = "1543-8384",
publisher = "American Chemical Society",
number = "7",

}

TY - JOUR

T1 - Chitosan-based thermoreversible hydrogel as an in Vitro tumor microenvironment for testing breast cancer therapies

AU - Tsao, Ching Ting

AU - Kievit, Forrest M

AU - Wang, Kui

AU - Erickson, Ariane E.

AU - Ellenbogen, Richard G.

AU - Zhang, Miqin

PY - 2014/7/7

Y1 - 2014/7/7

N2 - Breast cancer is a major health problem for women worldwide. Although in vitro culture of established breast cancer cell lines is the most widely used model for preclinical assessment, it poorly represents the behavior of breast cancers in vivo. Acceleration of the development of effective therapeutic strategies requires a cost-efficient in vitro model that can more accurately resemble the in vivo tumor microenvironment. Here, we report the use of a thermoreversible poly(ethylene glycol)-g-chitosan hydrogel (PCgel) as an in vitro breast cancer model. We hypothesized that PCgel could provide a tumor microenvironment that promotes cultured cancer cells to a more malignant phenotype with drug and immune resistance. Traditional tissue culture plates and Matrigel were applied as controls in our studies. In vitro cellular proliferation and morphology, the secretion of angiogenesis-related growth factors and cytokines, and drug and immune resistance were assessed. Our results show that PCgel cultures promoted tumor aggregate formation, increased secretion of various angiogenesis- and metastasis-related growth factors and cytokines, and increased tumor cell resistance to chemotherapeutic drugs and immunotherapeutic T cells. This PCgel platform may offer a valuable strategy to bridge the gap between standard in vitro and costly animal studies for a wide variety of experimental designs.

AB - Breast cancer is a major health problem for women worldwide. Although in vitro culture of established breast cancer cell lines is the most widely used model for preclinical assessment, it poorly represents the behavior of breast cancers in vivo. Acceleration of the development of effective therapeutic strategies requires a cost-efficient in vitro model that can more accurately resemble the in vivo tumor microenvironment. Here, we report the use of a thermoreversible poly(ethylene glycol)-g-chitosan hydrogel (PCgel) as an in vitro breast cancer model. We hypothesized that PCgel could provide a tumor microenvironment that promotes cultured cancer cells to a more malignant phenotype with drug and immune resistance. Traditional tissue culture plates and Matrigel were applied as controls in our studies. In vitro cellular proliferation and morphology, the secretion of angiogenesis-related growth factors and cytokines, and drug and immune resistance were assessed. Our results show that PCgel cultures promoted tumor aggregate formation, increased secretion of various angiogenesis- and metastasis-related growth factors and cytokines, and increased tumor cell resistance to chemotherapeutic drugs and immunotherapeutic T cells. This PCgel platform may offer a valuable strategy to bridge the gap between standard in vitro and costly animal studies for a wide variety of experimental designs.

KW - breast cancer

KW - chitosan

KW - hydrogel

KW - malignancy

KW - microenvironment

UR - http://www.scopus.com/inward/record.url?scp=84903954051&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84903954051&partnerID=8YFLogxK

U2 - 10.1021/mp5002119

DO - 10.1021/mp5002119

M3 - Article

VL - 11

SP - 2134

EP - 2142

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

IS - 7

ER -