Gold nanoparticles inhibit activation of cancer-associated fibroblasts by disrupting communication from tumor and microenvironmental cells

Yushan Zhang; Chandra Kumar Elechalawar; Md Nazir Hossen; Emmy R Francek; Anindya Dey; Stefan Wilhelm; Resham Bhattacharya; Priyabrata Mukherjee

doi:10.1016/j.bioactmat.2020.08.009

Gold nanoparticles inhibit activation of cancer-associated fibroblasts by disrupting communication from tumor and microenvironmental cells

Bioact Mater. 2020 Sep 1;6(2):326-332. doi: 10.1016/j.bioactmat.2020.08.009. eCollection 2021 Feb.

Authors

Yushan Zhang^{1

2}, Chandra Kumar Elechalawar^{1

2}, Md Nazir Hossen^{1

2}, Emmy R Francek³, Anindya Dey^{2

4}, Stefan Wilhelm^{2

3

5}, Resham Bhattacharya^{2

4}, Priyabrata Mukherjee^{1

2}

Affiliations

¹ Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
² Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
³ Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK, 73019, USA.
⁴ Department of Obstetrics and Gynecology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
⁵ Institute for Biomedical Engineering, Science, and Technology (IBEST), Norman, OK, 73019, USA.

Abstract

Cancer-associated fibroblasts (CAFs) are a major constituent of the tumor microenvironment (TME) and an important contributor to cancer progression and therapeutic resistance. Regulation of CAF activation is a promising strategy to influence cancer outcomes. Here, we report that ovarian cancer cells (OCs) and TME cells promote the activation of ovarian CAFs, whereas gold nanoparticles (GNPs) of 20 nm in diameter inhibit the activation, as demonstrated by the changes in cell morphology, migration, and molecular markers. GNPs exert the effect by altering the levels of multiple fibroblast activation or inactivation proteins, such as TGF-β1, PDGF, uPA and TSP1, secreted by OCs and TME cells. Thus, GNPs represent a potential tool to help understand multicellular communications existing in the TME as well as devise strategies to disrupt the communication.

Keywords: Cancer-associated fibroblast (CAF); Fibroblast activation; Gold nanoparticle (GNP); Migration; Morphology; Tumor microenvironment (TME).

Abstract

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