Abstract
Recent studies have implicated the roles of cancer stem like cells (CSCs) in cancer metastasis. However, very limited knowledge exists at the molecular and cellular level to target CSCs for prevention of cancer metastasis. In this study, we examined the roles of contractile dynamics of CSCs in cell invasion and delineated the underlying molecular mechanisms of their distinct cell invasion potential. Using de-adhesion assay and atomic force microscopy, we show that CSCs derived from melanoma and breast cancer cell lines exhibit increased contractility compared to non-CSCs across all tumor types. In addition, CSCs possess increased ECM remodeling capacity as quantified by collagen degradation assay. More importantly, pharmacological blockade of Rho-associated protein kinase completely abolished the contractility and collagen degradation capacity of both CSCs and non-CSCs. In conclusion, our study demonstrates the importance of cell contractility in regulating invasiveness of CSCs and suggests that pharmacological targeting of ROCK pathway represents a novel strategy for targeting both CSCs and bulk population for the treatment of cancer metastasis.
Highlights
Surgical removal of primary tumors is effective in treating localized tumors, treating cancer metastasis remains a formidable challenge
We examined the roles of contractile dynamics of Cancer stem like cells (CSC) in cell invasion and delineated the underlying molecular mechanisms of their distinct cell invasion potential
Pancreatic cell lines with higher contractility secrete increased levels of matrix metalloproteases (MMPs) and show higher invasion capacity [13]. It remains unknown if biophysical characteristics, especially contractile dynamics of CSCs are distinct compared to the bulk tumor population and contribute in CSC mediated cell invasion
Summary
Surgical removal of primary tumors is effective in treating localized tumors, treating cancer metastasis remains a formidable challenge. Contractile dynamics of a tumor cell represents one of the most important biophysical properties that regulates metastasis and invasion ability [6], and is closely associated with cell spreading and cell adhesion properties [7]. Increased cell contractility in breast cancer is associated with cell invasion through dense interstitial matrices by allowing cells to squeeze through matrix pores and in intravasation and extravasation [8]. Pancreatic cell lines with higher contractility secrete increased levels of matrix metalloproteases (MMPs) and show higher invasion capacity [13]. It remains unknown if biophysical characteristics, especially contractile dynamics of CSCs are distinct compared to the bulk tumor population and contribute in CSC mediated cell invasion
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