Researchers from IIT Bombay have found a novel pathway that is responsible for the progress of cancer metastasis — spread of cancer cells from its primary site of origin to new areas of the body. The finding holds potential in controlling metastasis to reduce cancer deaths. The study was published in the journal Oncotarget.
Surgical removal of primary tumours has long been used as a standard treatment for localised tumours, but treating cancer metastasis remains a formidable challenge. “Cancer stem cells (CSCs) are one cause of cancer metastasis. However, there is no study done so far to examine the impact of biophysical properties of cancer stem cells in cancer metastasis,” says Dr. Rahul Purwar, Assistant Professor at Department of Biosciences & Bioengineering, IIT Bombay.
Contractile dynamics of a tumour cell represents one of the most important biophysical properties and is closely associated with cell spreading and cell adhesion properties of tumour cell. Increased cell contractility in breast cancer can initiate the escape of cancerous cells from their primary sites to distant organs, that is, metastasis.
Dr. Purwar’s investigating team as well as other, earlier researchers have shown a close relationship between cell contractility (ability of cells to contract) and invasiveness in breast cancer cells, ovarian cancer cells and melanoma cells. Increased contractility is correlated with increased migration of cells which helps in metastasis.
However, it remains unknown whether contractile dynamics of CSCs are distinct as compared to the bulk tumour population and contribute in CSC-mediated metastasis.
Study lead author Dr. Purwar explains that “With this study, we identified a distinct pathway which CSCs use to invade the extracellular matrix and metastasise to other organs. Surprisingly, we observed that blockade of this pathway by pharmaceutical drugs completely abolished the invasion of CSCs as well as other tumour cells. Thus, targeting this distinct pathway may lead to the development of robust and long-term remission of cancer metastasis’’.
Cell contractility is regulated by two groups of enzymes including myosin light chain kinase (MLCK) and Rho associated protein kinase (ROCK). The team found that pharmacological targeting of ROCK prevents contractility and cell invasion potential of both CSCs and non-cancer stem cells, and is therefore a novel strategy for the treatment of cancer metastasis.
“Our work provides the first evidence of targeting biophysical properties of cancer stem cells for controlling metastatic cancer. However, further work is required to translate our findings before it goes to clinic,” he says.