I have always asked “how and why cells migrate in our body? how this process is regulated“? Back in medical school i learned about physiological migration of immune cells from bone marrow and within tissues.
Chemotaxis – what a magical power behind cell motility within organism!! Later on, when I started studying biology of blood stem and progenitor cells, I realized that we don’t know much about how these cells migrate or home to the niche. At the same time, I realized that an ability to manipulate of stem/progenitor cells trafficking would be an incredible tool.
Pathotropism is an ability of progenitor/stem cells from the bone marrow to specifically migrate to pathological sites, such as an inflamed area or a tumor.
Some molecules and axises (such as CXCR4-SDF-1, HIF-1, SCF-cKit, HGF-cMet…) are known to make hematopoietic progenitors or stem cell migrate to inflammatory or ischemic sites. CXCR4-SDF-1 interaction is also well known like an axis for tumor metastasis. Also some adult stem cells, neural and mesenchymal for instance, were shown to specifically migrate to tumor site. This ability has been exploited to selectively deliver a therapeutic gene to metastatic solid tumors. Researches hope that expression of an appropriate transgene at tumor loci, delivered by cell vehicle, might mediate killing of the tumor mass and/or cures of metastatic disease.
So, we know that neural and mesenchymal stem cells could be used as vehicles for delivering therapeutic agents (including genes) to tumors. However, signals required for recruitment of these cells to tumor remain unknown.
Recent discovery, published in online version of Stem Cells journal, describe 2 molecules which are mediate migration of both – neural and mesenchymal stem cell tropism to malignant tumor. Overexpression of Urokinase Plasminogen Activator (uPA) and its receptor, uPAR (=CD87) in different malignant solid tumor cell lines led to increased migration of both types of cells. In another experiment, depletion of uPA led to inhibition of stem cell migration. Also authors identify some cytokines in tumor-conditioned media (such us IL-6, IL-8 and MCP-1), which could be chemoattractants and play roles in uPA-uPAR dependent migration.
It was shown before that soluble uPAR is involved in G-CSF induced mobilization of hematopoietic stem cells from bone marrow. Importantly, this study shows that uPA-uPAR is involved in regulation of both mesenchymal and neural stem cell migration to tumor. Now we have more evidence to study this phenomenon further. It is notable that the work was done only in vitro system. Before starting to use this system in preclinical models, we still have to check how it works in a series of in vivo experiments. Finally i want to conclude that as we learn about a magic behind stem cell migration in our body, it will provide us with a possibility to manipulate trafficking of injected cells to benefit patients.
Stem Cells 2008, Epub. Apr 10
picture credit: Charles J. Dimitroff lab (Harvard Med School).