Model of collective detachment in high-grade serous ovarian cancer demonstrates that tumor spheroids produce ECM to support metastatic processes-Reference-Cited by-同舟云学术

Model of collective detachment in high-grade serous ovarian cancer demonstrates that tumor spheroids produce ECM to support metastatic processes

Published:2023-02-28 Issue:1 Volume:7 Page:
ISSN:2473-2877
Container-title:APL Bioengineering
language:en
Short-container-title:

Author:

Micek Hannah M.¹^ORCID,Rosenstock Lauren¹^ORCID,Ma Yicheng¹^ORCID,Hielsberg Caitlin¹^ORCID,Montemorano Lauren²^ORCID,Gari Metti K.³⁴^ORCID,Ponik Suzanne M.⁴⁵^ORCID,Kreeger Pamela K.¹²⁴⁵^ORCID

Affiliation:

1. Department of Biomedical Engineering, University of Wisconsin-Madison 1 , Madison, Wisconsin 53705, USA

2. Department of Obstetrics and Gynecology, University of Wisconsin School of Medicine and Public Health 2 , Madison, Wisconsin 53705, USA

3. Molecular and Cellular Pharmacology Training Program, University of Wisconsin School of Medicine and Public Health 3 , Madison, Wisconsin 53705, USA

4. Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health 4 , Madison, Wisconsin 53705, USA

5. University of Wisconsin Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health 5 , Madison, Wisconsin 53705, USA

Abstract

High-grade serous ovarian cancer (HGSOC) metastasizes through transcoelomic spread, with both single cells and spheroids of tumor cells observed in patient ascites. These spheroids may form through single cells that detach and aggregate (Sph-SC) or through collective detachment (Sph-CD). We developed an in vitro model to generate and separate Sph-SC from Sph-CD to enable study of Sph-CD in disease progression. In vitro-generated Sph-CD and spheroids isolated from ascites were similar in size (mean diameter 51 vs 55 μm, p > 0.05) and incorporated multiple ECM proteins. Using the in vitro model, nascent protein labeling, and qRT-PCR, we determined that ECM was produced after detachment. As fibronectin plays a key role in many cell adhesion events, we confirmed that inhibiting RGD-based adhesion or fibronectin assembly reduced Sph-CD-mesothelial adhesion strength under shear stress. Our model will enable future studies to determine factors that favor formation of Sph-CD, as well as allow investigators to manipulate Sph-CD to better study their effects on HGSOC progression.

Funder

National Cancer Institute

Publisher

AIP Publishing

Subject

Biomedical Engineering,Biomaterials,Biophysics,Bioengineering

Link

https://pubs.aip.org/aip/apb/article-pdf/doi/10.1063/5.0132254/16773798/016111_1_online.pdf

Reference39 articles.

1. National Cancer Institute, see www.seer.cancer.gov for “Surveillance, Epidemiology, and End Results (SEER) Program.”

2. Multicellular spheroids in ovarian cancer metastases: Biology and pathology

3. Constitutive activation of integrin αvβ3 contributes to anoikis resistance of ovarian cancer cells