Modulation of cancer stemness property in head and neck cancer cells via circulatory fluid shear stress

Circulating tumor cells (CTCs) known as tumor cells dissociate from primary tumor sites and travel to secondary tumor sites via vasculature during cancer metastasis. Accumulated clinical evidence has shown that the presence of CTCs may be considered as a major prognostic marker and may increase the risk of head and neck cancer metastasis. Moreover, partial CTCs might consist of cancer stem cells (CSCs) which play critical roles in tumor recurrence and chemo-resistance. However, the connection between CTCs and CSCs remains uncertain. In this study, a physiologically bio-mimicking fluid shear stress (FSS) circulatory system was developed to precisely study the relationship between CTCs and CSCs. The properties of human head and neck cancer cells (HNCs) were studied under a continuous circulatory FSS microenvironment. The results revealed that the cell viability of HNCs was inversely correlated to FSS magnitude and time. The level of intracellular reactive oxygen species in HNCs was increased after circulating the cells under FSS. Moreover, cancer stemness related gene expression and aldehyde dehydrogenase (ALDH) activity were significantly elevated in the FSS survived HNCs. Also, results from chemo-resistance assay showed that the FSS survived HNCs expressed higher resistance to anti-cancer drugs. Our approach is the first report to provide an in vitro fully continuous FSS circulatory system on modulating cancer stemness property of HNCs. Better understanding of the modulation of cancer stemness property in CTCs is expected to advancement of effective therapeutic strategies for cancer metastasis.