Drug & Device Development

Fractalkine curbs metastatic colon cancer in mice

Last Updated: 2007-03-27 13:05:16 -0400 (Reuters Health)

By David Douglas

NEW YORK (Reuters Health) - The chemokine fractalkine has powerful anti-tumor activity in a mouse model of metastatic colon cancer, French researchers report in the March issue of Gut.

Senior investigator Dr. Heidy Schmid-Alliana told Reuters Health that "our preliminary experiments performed in models of subcutaneous implantation of several tumor cell types, with intra-tumoral injections of fractalkine-coding plasmids, produced highly promising results with a marked reduction in tumor size."

Dr. Schmid-Alliana, of INSERM U638, Nice, and colleagues note that the agent presents as both a secreted and a membrane-anchored form. Using murine models of skin tumors and liver and pulmonary metastasis, the researchers compared the extent of tumor development in C26 colon cancer cells expressing fractalkine in its molecular forms.

Native fractalkine reduced the tumor size by 93% in the skin and by 99% in the orthotopic models. Both soluble and membrane-bound fractalkine reduced tumor development in skin by 66%.

The soluble form reduced liver and lung metastases by 96%. However, the membrane-bound variant had a barely significant effect and promoted tumor growth in the lungs.

The researchers conclude that fractalkine "drastically reduces" metastatic potential in the two physiological target organs. "Both molecular forms contribute to its antitumour potential, but exhibit differential effects on tumour development depending on the target tissue," they add.

Dr. Martina Brueckmann of the University of Heidelberg, Germany, author of an accompanying editorial, told Reuters Health that little is known about suitable techniques for immune therapy with fractalkine.

However, she concluded, the efficacy of this reported approach "deserves further research in experimental and especially in human clinical trials to improve immunological treatment modalities of metastatic colon cancer."

Gut 2007;56:365-372.