Abstract
ABSTRACTProviding an external mechanical stress to cancer cells seems to be an effective approach to treat cancer locally. Numbers of reports on cancer cell death subjected to mechanical stress loading are increasing, but they are more focused on apoptosis. Inducing necrosis is also important in attracting more immune cells to the cancer site via the release of danger-associated molecular patterns from cancer cells. Here we applied dynamic compression to breast cancer cells with a low frequency (0.1–30 Hz) and for a short duration (30–300 s) and they resulted in a mixed mode of apoptosis and necrosis dominant with necrotic cell death, which we call mechanical stress-induced cell death (MSICD). The necrotic cell damage of mechanically treated breast cancer cells increased in a force-dependent and time-dependent manner while a trend of frequency-independent MSICD was observed.
Highlights
Various types of stress can trigger cells to undergo apoptotic and/or necrotic cell death and many researchers have claimed that mechanical stress (MS) was one of the contributors to this event (Mayr et al, 2000; Cheng et al, 2009; Kong et al, 2013; Lien et al, 2013; Gao et al, 2014; Andarawis-Puri et al, 2014)
The Jain group reported cell damage under quasi-static compression loading; they found (i) an increase in the apoptosis of cancer cells is observed under increasing MS when studying the effects of quasi-static MS on the growth and proliferation of murine mammary carcinoma cell lines (67NR and EMT6) (Cheng et al, 2009); (ii) excessive stresses (>5.8 mmHg) triggered apoptosis and impeded cell migration (Tse et al, 2012); (iii) the stress-induced growth inhibition of plateau-phase spheroids is accompanied by decreased apoptosis (Helmlinger et al, 1997); and (iv) the growth-induced solid stress by the quasi-static compression leads to hypoxia, promotes tumor progression, immunosuppression and lowers the efficacy of chemo, radio- and immunotherapies (Stylianopoulos et al, 2012)
Among MDA-MB-231 specimens treated with 40 μm of displacement for 300 s, the MS-induced cell death (MSICD) rate dramatically increased with the distance (r defined in Fig. 3A) from the center of the culture dish (Fig. 5)
Summary
Various types of stress can trigger cells to undergo apoptotic and/or necrotic cell death and many researchers have claimed that mechanical stress (MS) was one of the contributors to this event (Mayr et al, 2000; Cheng et al, 2009; Kong et al, 2013; Lien et al, 2013; Gao et al, 2014; Andarawis-Puri et al, 2014). These MS varied from static stress (normal compression and shear stress) to cyclic stress loading. The Jain group reported cell damage under quasi-static compression loading; they found (i) an increase in the apoptosis of cancer cells is observed under increasing MS when studying the effects of quasi-static MS on the growth and proliferation of murine mammary carcinoma cell lines (67NR and EMT6) (Cheng et al, 2009); (ii) excessive stresses (>5.8 mmHg) triggered apoptosis and impeded cell migration (Tse et al, 2012); (iii) the stress-induced growth inhibition of plateau-phase spheroids is accompanied by decreased apoptosis (Helmlinger et al, 1997); and (iv) the growth-induced solid stress by the quasi-static compression leads to hypoxia, promotes tumor progression, immunosuppression and lowers the efficacy of chemo-, radio- and immunotherapies (Stylianopoulos et al, 2012).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
