Circulating prostate cancer cells have differential resistance to fluid shear stress-induced cell death.

Jacob M Hope,Jenna A Dombroski,Matthew R Bersi,Rebecca S Pereles,Michael R King,W David Merryman,Andrea B Clinch

doi:10.1242/jcs.251470

Abstract

ABSTRACTCirculating tumor cells (CTCs) are exposed to fluid shear stress (FSS) of greater than 1000 dyn/cm2 (100 Pa) in circulation. Normally, CTCs that are exposed to FSS of this magnitude die. However, some CTCs develop resistance to this FSS, allowing them to colonize distant organs. We explored how prostate CTCs can resist cell death in response to forces of this magnitude. The DU145, PC3 and LNCaP human prostate cancer cell lines were used to represent cells of different metastatic origins. The cell lines were briefly treated with an average FSS of 3950 dyn/cm2 (395 Pa) using a 30 G needle and a syringe pump. DU145 cells had no change in cell viability, PC3 cells had some cell death and LNCaP cells exhibited significant cell death. These cell death responses correlated with increased cell membrane damage, less efficient membrane repair and increased stiffness. Additionally, FSS treatment prevented the LNCaP FSS-sensitive cell line from forming a growing tumor in vivo. This suggests that these properties play a role in FSS resistance and could represent potential targets for disrupting blood-borne metastasis.

Highlights

Metastasis accounts for ∼90% of cancer-related deaths (Seyfried and Huysentruyt, 2013)
fluid shear stress (FSS) treatment induces cell death in PC3 and LNCaP cells To determine whether the different prostate cancer cells exhibit different sensitivities to FSS, the cancer cells were treated with 0–10 pulses of FSS
A previous study determined that the PC3 prostate cancer cell lines are innately more resistant to FSS than healthy prostate epithelial cells, suggesting that FSS resistance contributes to metastasis (Barnes et al, 2012)

Summary

Introduction

Metastasis accounts for ∼90% of cancer-related deaths (Seyfried and Huysentruyt, 2013). Cancer metastasis occurs when cancer cells detach from the primary tumor and invade the surrounding matrix. The cells enter the circulation by intravasating through the endothelial cell wall. Once the cells enter the circulatory system, they are collectively referred to as circulating tumor cells (CTCs). After the CTCs disseminate throughout the body, they bind to endothelial cells on the vessel wall and extravasate into secondary sites. The cancer cells proliferate to form a secondary tumor (Sahai, 2007; Valastyan and Weinberg, 2011; van Zijl et al, 2011)

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