Researchers in the US have used ECM-coated poly(ε-caprolactone) as a scaffold to mimic the pre-metastatic niche, which is a site usually within a solid organ that cancer cells would colonize. Their laboratory model of this niche could reveal what factors and conditions by which breast, pancreatic, or prostate cancer cells would find their way into the lungs or liver, and ultimately provide a view to finding new ways to block metastasis.
The process of cancer spreading from a primary tumor to other parts of the body is referred to as metastasis. It is difficult to treat cancer that has spread beyond the primary site, and survival rates for patients with metastases are very low and it is often at this point that the disease is referred to as untreatable.
Lonnie Shea of the University of Michigan, Ann Arbor, and colleagues explain that metastasis occurs as tumor cells "colonize" solid organs such as bone, liver, or lung, and the sites to which the cells colonize is referred to as the pre-metastatic niche, which is a complex microenvironment consisting partially of extracellular matrix (ECM) proteins. That cancer cells regularly colonize specific organs indicates that metastasis is not random and that the cancer cells associate with particular properties within the organ. The pre-metastatic niche creates an environment that enables colonization by the cancer cells and their subsequent growth that can compromise the function of that organ.
The team's biomaterials approach to investigating metastasis involved using a mouse model of breast cancer and implanting microporous PCL scaffolds in laboratory animals to see how quickly and easily breast cancer cells might be recruited to colonize the scaffold. In order to control colonization, the team had coated different scaffolds with various ECM proteins, including decellularized lung and liver matrix from tumor-bearing mice.
The researchers used mass spectrometry proteomics techniques to characterize the organ matrices and demonstrated that the enzyme myeloperoxidase was a significant ECM protein that contributes to colonization. The addition of myeloperoxidase to the scaffold enhanced the recruitment of cancer cells to the implant.
"Our scaffold provides a platform to identify novel contributors to colonization and allows for the capture of colonizing tumor cells for a variety of downstream clinical applications," the team reports in the journal Acta Biomaterialia [Shea et al., Acta Biomaterialia (2016) DOI: 10.1016/j.actbio.2016.01.043]. There are many factors that can be involved in the pre-metastatic niche, such as the mechanical properties and topography of the niche, immune cells and immunomodulators, and integrin interactions with the surrounding matrix, the team reports.
David Bradley blogs at Sciencebase Science Blog and tweets @sciencebase, he is author of the bestselling science book "Deceived Wisdom".