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

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 develope...

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Autores principales: Micek, Hannah M., Rosenstock, Lauren, Ma, Yicheng, Hielsberg, Caitlin, Montemorano, Lauren, Gari, Metti K., Ponik, Suzanne M., Kreeger, Pamela K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AIP Publishing LLC 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9977464/
https://www.ncbi.nlm.nih.gov/pubmed/36875739
http://dx.doi.org/10.1063/5.0132254
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author Micek, Hannah M.
Rosenstock, Lauren
Ma, Yicheng
Hielsberg, Caitlin
Montemorano, Lauren
Gari, Metti K.
Ponik, Suzanne M.
Kreeger, Pamela K.
author_facet Micek, Hannah M.
Rosenstock, Lauren
Ma, Yicheng
Hielsberg, Caitlin
Montemorano, Lauren
Gari, Metti K.
Ponik, Suzanne M.
Kreeger, Pamela K.
author_sort Micek, Hannah M.
collection PubMed
description 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.
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spelling pubmed-99774642023-03-02 Model of collective detachment in high-grade serous ovarian cancer demonstrates that tumor spheroids produce ECM to support metastatic processes Micek, Hannah M. Rosenstock, Lauren Ma, Yicheng Hielsberg, Caitlin Montemorano, Lauren Gari, Metti K. Ponik, Suzanne M. Kreeger, Pamela K. APL Bioeng Articles 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. AIP Publishing LLC 2023-02-28 /pmc/articles/PMC9977464/ /pubmed/36875739 http://dx.doi.org/10.1063/5.0132254 Text en © 2023 Author(s). https://creativecommons.org/licenses/by/4.0/All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Articles
Micek, Hannah M.
Rosenstock, Lauren
Ma, Yicheng
Hielsberg, Caitlin
Montemorano, Lauren
Gari, Metti K.
Ponik, Suzanne M.
Kreeger, Pamela K.
Model of collective detachment in high-grade serous ovarian cancer demonstrates that tumor spheroids produce ECM to support metastatic processes
title Model of collective detachment in high-grade serous ovarian cancer demonstrates that tumor spheroids produce ECM to support metastatic processes
title_full Model of collective detachment in high-grade serous ovarian cancer demonstrates that tumor spheroids produce ECM to support metastatic processes
title_fullStr Model of collective detachment in high-grade serous ovarian cancer demonstrates that tumor spheroids produce ECM to support metastatic processes
title_full_unstemmed Model of collective detachment in high-grade serous ovarian cancer demonstrates that tumor spheroids produce ECM to support metastatic processes
title_short Model of collective detachment in high-grade serous ovarian cancer demonstrates that tumor spheroids produce ECM to support metastatic processes
title_sort model of collective detachment in high-grade serous ovarian cancer demonstrates that tumor spheroids produce ecm to support metastatic processes
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9977464/
https://www.ncbi.nlm.nih.gov/pubmed/36875739
http://dx.doi.org/10.1063/5.0132254
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