The Tumor-Host Genomics project links together the resources of five European leading-edge laboratories studying major signaling pathways in mesenchymal and hematopoietic cells, forming a concerted effort to understand tumor-host interactions, and to identify novel therapeutic targets.

The European Union will fund the project with a total of 2.7 million ?‚¬ during the next three years. The project is coordinated by Dr. Petri Salven from the University of Helsinki. The other participating principal investigators are Dr. Kari Alitalo and Dr. Jussi Taipale, also form the University of Helsinki, Dr. Peter ten Dijke from Leiden University Medical Center in the Netherlands, and Dr. Luigi Naldini from the San Raffaele Telethon Insitute for Gene Therapy in Italy.

In addition to oncogenic mutations that act cell-autonomously, tumor cell growth depends on interactions with its microenvironment. Tumor microenvironment consists of cells of hematopoietic and mesenchymal origin, including inflammatory cells, stem and progenitor cells, fibroblasts, endothelial cells and vascular mural cells. Tumor cell growth is known to depend on the interaction of tumor cells with such stromal cells. For example, growing tumor needs to recruit normal endothelial and vascular mural cells to form its blood vessels.

The Tumor-Host Genomics project will develop novel advanced functional genomics instruments, technologies and methods to study tumor-host interactions in cancer, and apply these techniques to the identification of molecules and processes in normal cells which could be targeted by novel anti-cancer therapeutic agents. The ultimate goal of the project is to unravel and validate new targets for anticancer therapy, and new strategies for delivering therapy to tumors.

"We are studying the molecular and cellular interactions between the normal, benign cells of the tumor microenvironment, and the cancer cells. These interactions represent an attractive target for cancer therapy, because normal cells are genetically stable, and would not be expected to develop resistance to therapeutic agents", says Dr. Salven, the coordinator for the project.

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These experiments demonstrate that a significant portion of satellite or SP cells is derived from the somites. However, not all SP cells were derived from the somites, indicating that some may be derived from the bone marrow.

When the researchers went on to compare SP cells derived from somite to SP cells potentially derived from bone marrow, they found that the somite-derived SP cells were much better at making muscle.

Duchenne's muscular dystrophy is caused when the dystrophin gene is defective. Medical researchers have been looking for ways to use SP and satellite cells to deliver healthy copies of dystrophin to the damaged muscle in Duchenne's patients.

Potentially, satellite or SP cells with a healthy copy of dystrophin could be injected into the circulatory system to home to and repair dystrophic muscle.

While satellite cells are highly myogenic (effective in muscle repair) from inside the body, they are inefficient in forming muscle when injected into mice. SP cells have been shown to produce a small amount of muscle when injected into dystrophic mice and may be candidates for delivering dystrophin, according to Kardon.

Using SP cells derived from somites may further increase their efficiency in repairing diseased muscle. But a lot of work remains to be done.

"We need to find highly myogenic cells that can be delivered systemically, such as by injection, and that can both home to and repair all the muscles of the body," Kardon said.

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