Presence of stromal cells in a bioengineered tumor microenvironment alters glioblastoma migration and response to STAT3 inhibition

R. Marisol Herrera-Perez, Sherry L. Voytik-Harbin, Jann N Sarkaria, Karen E. Pollok, Melissa L. Fishel, Jenna L. Rickus

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Despite the increasingly recognized importance of the tumor microenvironment (TME) as a regulator of tumor progression, only few in vitro models have been developed to systematically study the effects of TME on tumor behavior in a controlled manner. Here we developed a three-dimensional (3D) in vitro model that recapitulates the physical and compositional characteristics of Glioblastoma (GBM) extracellular matrix (ECM) and incorporates brain stromal cells such as astrocytes and endothelial cell precursors. The model was used to evaluate the effect of TME components on migration and survival of various patient-derived GBM cell lines (GBM10, GBM43 and GBAM1) in the context of STAT3 inhibition. Migration analysis of GBM within the 3D in vitro model demonstrated that the presence of astrocytes significantly increases the migration of GBM, while presence of endothelial precursors has varied effects on the migration of different GBM cell lines. Given the role of the tumor microenvironment as a regulator of STAT3 activity, we tested the effect of the STAT3 inhibitor SH-4-54 on GBM migration and survival. SH-4-54 inhibited STAT3 activity and reduced 3D migration and survival of GBM43 but had no effect on GBM10. SH-4-54 treatment drastically reduced the viability of the stem-like line GBAM1 in liquid culture, but its effect lessened in presence of a 3D ECM and stromal cells. Our results highlight the interplay between the ECM and stromal cells in the microenvironment with the cancer cells and indicate that the impact of these relationships may differ for GBM cells of varying genetic and clinical histories.

Original languageEnglish (US)
Article numbere0194183
JournalPLoS One
Volume13
Issue number3
DOIs
StatePublished - Mar 1 2018

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Tumor Microenvironment
stromal cells
Glioblastoma
Stromal Cells
Tumors
neoplasms
extracellular matrix
Extracellular Matrix
astrocytes
Cells
Astrocytes
Survival
cell lines
physical models
Cellular Microenvironment
Endothelial cells
Cell Line
Neoplasms
endothelial cells
Brain

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Presence of stromal cells in a bioengineered tumor microenvironment alters glioblastoma migration and response to STAT3 inhibition. / Marisol Herrera-Perez, R.; Voytik-Harbin, Sherry L.; Sarkaria, Jann N; Pollok, Karen E.; Fishel, Melissa L.; Rickus, Jenna L.

In: PLoS One, Vol. 13, No. 3, e0194183, 01.03.2018.

Research output: Contribution to journalArticle

Marisol Herrera-Perez, R. ; Voytik-Harbin, Sherry L. ; Sarkaria, Jann N ; Pollok, Karen E. ; Fishel, Melissa L. ; Rickus, Jenna L. / Presence of stromal cells in a bioengineered tumor microenvironment alters glioblastoma migration and response to STAT3 inhibition. In: PLoS One. 2018 ; Vol. 13, No. 3.
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