The process of intratumor vasculogenesis can be sustained by endothelial differentiation of normal or cancer stem cells present in the tissue. In the present study, Shen and collaborators demonstrate that pre-cancer stem cells can differentiate in endothelial cells and contribute to tumor vasculogenesis.
We recently showed the vasculogenic property of human CD105+ tumor stem/progenitor cells from renal carcinomas and of CD44+/CD24- tumor stem/progenitor cells from breast carcinomas. In these papers, tumor stem cells were shown to be bipotent, being able to differentiate into tumor epithelial and endothelial cells (Bussolati B et al. [PMID: 18614581] FASEB J. 2008; Bussolati B et al. [PMID: 18410528] J Cell Mol Med. 2008). In agreement with the hypothesis here proposed that the vasculogenic differentiation of cancer stem cells could be relevant in the early phase of tumor growth, we also report that breast or renal tumor stem cells injected within Matrigel and recovered after few days, generate small cluster of tumors together with a large number of little vessels.
The capacity of cancer stem cells to differentiate in different cell populations of the tumor can be ascribed to the stem nature of tumor stem cells and supports the idea of their origin from mutated stem cells of the tissue. Indeed, the ability of cancer stem cells to differentiate in multiple lineages has been shown for melanoma-derived stem/progenitor cells that are able to differentiate in multiple mesenchymal lineages, such as adypocitic, osteocytic, and chondrocytic lineages (Fang D et al. [PMID: 16230395] Cancer Res. 2005). In this line, mutated mesenchymal stem cells were shown to generate not only tumors, but also tumor adipose tissue and tumor vasculature (Li H et al. [PMID: 18006834] Cancer Res. 2007).
Tumor vessels have been shown to be genetically unstable, to differ from normal vessel endothelial cells at molecular and functional levels and, in some instances, to share a tumor specific genetic alteration or oncogene (Hida K et al. Cancer Sci 2008 [PMID: 18167133]). The origin of endothelial cells by cancer stem cells could explain these results. A similar concept could also be true for stromal cells, that have been reported to have genetic alterations (Pelham RJ et al. Proc Natl Acad Sci U S A. 2006 [PMID: 17167050]).
Taking together all these considerations, the vasculogenic potential of cancer or pre-cancer stem cells may support the concept that this population orchestrates the tumor growth and, beside the tumor cells itself, generate the microenvironment that sustains the tumor malignancy.