Oncotarget

In The News - Press Releases


Oncotarget Cancer associated fibroblasts confer shear resistance to circulating tumor cell


FOR IMMEDIATE RELEASE
2020-03-27

Oncotarget Volume 11, Issue 12 reported that the observation that Cancer associated fibroblasts (CAFs) disseminate with Circulating Tumor Cells (CTCs) prompts the examination of the role of CAFs in CTC survival under physiological shear stress during the dissemination process using a clinically relevant, three-dimensional co-culture model.

In this study, the research team found that reactive CAFs induce shear resistance to prostate tumor cells via intercellular contact and soluble derived factors.

The reactive CAFs showed higher expression of -smooth muscle actin and fibroblast activation protein compared to differentiated CAFs, when co-cultured with PC cells at the same experimental conditions.

Dr. Michael R. King from the Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37202, USA said, "Prostate cancer (PC) is the second leading cause of cancer related death in western countries, with most of these deaths attributed to cancer metastasis."

"Prostate cancer (PC) is the second leading cause of cancer related death in western countries, with most of these deaths attributed to cancer metastasis."

- Dr. Michael R. King, Department of Biomedical Engineering, Vanderbilt University

Several studies have determined that CAFs play a critical role in promoting PC progression by inducing tumor cell growth, invasion, epithelial-to-mesenchymal transition, ADT resistance, and enhanced tumor cell colonization.

Demonstrated that CAFs can migrate together with circulating tumor cells as circulating cell aggregates.

Importantly, these prior studies demonstrated the presence of CAFs in the circulation and the significant role of circulating stroma cells in promoting cancer progression, however, the specific function of CAFs in the bloodstream has not been elucidated yet.

Figure 1: Characterization of DU145 and stromal cell co-culture in spheroid growth and composition. (A) Bright field images of DU145, DU145-CAF and DU145-NF spheroids after 24 hr in culture. Scale bar represents 200 μm. (B) Immunofluorescent staining of DU145, DU145-CAF and DU145-NF spheroids after 24 hr in culture (DU145 in green, fibroblast in red and nucleus in blue). Scale bar of 100 μm. (C) Bar chart represents the size distribution of DU145, DU145-CAF and DU145-NF spheroids at 0, 24, and 48 hr in culture (mean and range; n = 3 of two co-culture wells). Significance effect of DU145 and stromal cell co-culture (*P < 0.0498, **P < 0.0067, ***P < 0.0003 and ****P < 0.0001) in the size distribution of spheroids at 0, 24 and 48 hr in culture was calculated using two-way ANOVA. (D) Bar graph represents the spheroid concentration of DU145, DU145-CAF and DU145-NF spheroids at 0, 24 and 48 hr of growth (mean and S. D.; n = 3 of two co-culture wells). Non-significance (P < 0.9997) was calculated using two-way ANOVA. (E) Scatter dot chart represents the composition of cells per spheroid in different co-culture conditions (mean and S. D.; n = 3 of two co-culture wells). Significance (****P < 0.0001) was calculated via two-way ANOVA.

These authors hypothesize that CAFs confer resistance to high magnitude FSS to tumor cells in the circulation when the cells are incorporated into cell aggregates in collective migration units.

In the present study, using a 3D model, the authors determined that recently activated CAFs, termed reactive CAFs rather than differentiated CAFs, induced FSS resistance to PC cells by forming stable cell aggregates which can maintain their viability and proliferative capability.

The King Research Team concluded in their Oncotarget Research Paper, "we have demonstrated that reactive CAFs confer FSS resistance to prostate tumor cells in cellular aggregates via intercellular contacts as well as soluble derived factors. Importantly, this heterotypic cellular cluster can maintain the proliferative capability of prostate tumor cells within FSS. Indeed, reactive CAF cells are a key player in promoting the survival of tumor cells in the circulation, which suggests the importance of circulating CAF in the bloodstream as a biomarker for worse prognosis in metastatic disease as well as a promising target for novel cancer therapeutics."

Sign up for free Altmetric alerts about this article

DOI - https://doi.org/10.18632/oncotarget.27510

Full text - https://www.oncotarget.com/article/27510/text/

Correspondence to - Michael R. King - mike.king@vanderbilt.edu

Keywords - metastasis, cancer associated fibroblasts, circulating tumor cells, cytoprotection, collective migration

About Oncotarget

Oncotarget is a weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology.

To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with:

SoundCloud - https://soundcloud.com/oncotarget
Facebook - https://www.facebook.com/Oncotarget/
Twitter - https://twitter.com/oncotarget
LinkedIn - https://www.linkedin.com/company/oncotarget
Pinterest - https://www.pinterest.com/oncotarget/
Reddit - https://www.reddit.com/user/Oncotarget/

Oncotarget is published by Impact Journals, LLC please visit https://www.impactjournals.com/ or connect with @ImpactJrnls

Media Contact
MEDIA@IMPACTJOURNALS.COM
18009220957x105



Copyright © 2020 Impact Journals, LLC
Impact Journals is a registered trademark of Impact Journals, LLC