1. ¹Department of Morphological and Biomedical Sciences, Anatomy and Histology Section, University of Verona, Verona, Italy
2. ²Department of Molecular, Cellular and Animal Biology, Genetic Immunization laboratory, University of Camerino, Camerino, Macerata, Italy
3. ³Department of Clinical and Experimental Medicine, Haematology Section, University of Verona, Verona, Italy

Correspondence: Dr M Galiè, Department of Morphological and Biomedical Sciences, Anatomy and Histology Section, University of Verona, via Le grazie, 8, Verona, Verona 37134, Italy. E-mail: mirco@anatomy.univr.it

Received 25 May 2007; Revised 3 September 2007; Accepted 10 October 2007; Published online 12 November 2007.

Abstract

Tumor microenvironment in carcinomas recruits mesenchymal cells with an abnormal proangiogenic and invasive phenotype. It is not clear whether mesenchymal tumor cells (MTCs) derive from the activation of mature fibroblasts or from their stem cell precursors. However, stromal cell activation in tumors resembles in several aspects the mesenchymal rearrangement which normally occurs during reparative processes such as wound healing. Mesenchymal stem cells (MSCs) play a crucial role in developmental and reparative processes and have extraordinary proangiogenic potential, on the basis of which they are thought to show great promise for the treatment of ischemic disorders. Here, we show that MTCs have proangiogenic potential and that they share the transcriptional expression of the best-known proangiogenic factors with MSCs. We also found that MTCs and MSCs have the same molecular signature for stemness-related genes, and that when co-implanted with cancer cells in syngeneic animals MSCs determine early tumor appearance, probably by favoring the angiogenic switch. Our data (1) reveal crucial aspects of the proangiogenic phenotype of MTCs, (2) strongly suggest their stem origin and (3) signal the risk of therapeutic use of MSCs in tumor-promoting conditions.