The role of tumor-stroma interactions on desmoplasia and tumorigenicity within a microengineered 3D platform

Harpinder Saini, Kiarash Rahmani Eliato, Jaimeson Veldhuizen, Azadeh Zare, Mayar Allam, Casey Silva, Alex Kratz, Danh Truong, Ghassan Mouneimne, Joshua LaBaer, Robert Ros, Mehdi Nikkhah

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

The tumor microenvironment has been demonstrated to play a crucial role in modulating cancer progression. Amongst various cell types within the tumor microenvironment, cancer associated fibroblasts (CAFs) are in abundance, serving to modulate the biophysical properties of the stromal matrix, through excessive deposition of extracellular matrix (ECM) proteins that leads to enhanced tumor progression. There is still a critical need to develop a fundamental framework on the role of tumor-stromal cell interactions on desmoplasia and tumorigenicity. Herein, we developed a 3D microengineered organotypic tumor-stroma model incorporated with breast cancer cells surrounded by CAF-embedded collagen matrix. We further integrated our platform with atomic force microscopy (AFM) to study the dynamic changes in stromal stiffness during active tumor invasion. Our findings primarily demonstrated enhanced tumor progression in the presence of CAFs. Furthermore, we highlighted the crucial role of crosstalk between tumor cells and CAFs on stromal desmoplasia, where we identified the role of tumor-secreted PDGF-AA/-BB on elevated matrix stiffness. Inhibition of the activity of PDGFRs in CAFs led to attenuation of stromal stiffness. Overall, our work presents a well-controlled tumor microenvironment model capable of dissecting specific biophysical and biochemical signaling cues which lead to stromal desmoplasia and tumor progression.

Original languageEnglish (US)
Article number119975
JournalBiomaterials
Volume247
DOIs
StatePublished - Jul 2020
Externally publishedYes

Keywords

  • CAFs
  • Desmoplasia
  • Paracrine signaling
  • PDGF
  • Tumor microenvironment
  • Tumor-stromal crosstalk

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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  • Cite this

    Saini, H., Rahmani Eliato, K., Veldhuizen, J., Zare, A., Allam, M., Silva, C., Kratz, A., Truong, D., Mouneimne, G., LaBaer, J., Ros, R., & Nikkhah, M. (2020). The role of tumor-stroma interactions on desmoplasia and tumorigenicity within a microengineered 3D platform. Biomaterials, 247, [119975]. https://doi.org/10.1016/j.biomaterials.2020.119975