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(Circulation. 2002;105:112.)
© 2002 American Heart Association, Inc.

Basic Science Reports

Analysis of Mural Cell Recruitment to Tumor Vessels

Alexandra Abramsson, MSc; Örjan Berlin, MD, PhD; Hayk Papayan, PhD; Denise Paulin, PhD; Moshe Shani, PhD; Christer Betsholtz, PhD

From the Department of Medical Biochemistry, Göteborg University (A.A., C.B.), and the Department of Orthopedics, Sahlgrenska Hospital, Göteborg University (Ö.B.), Göteborg, Sweden; the Laboratoire de Biologie Moleculaire de la Differenciation, Université Denis Diderot Paris 7, Paris, France (H.P., D.P.); and the Institute of Animal Science, The Volcani Center, Bet Dagan, Israel (M.S.).

Correspondence to Christer Betsholtz, Department of Medical Biochemistry, Göteborg University, PO Box 440, SE 405 30 Göteborg, Sweden. E-mailchrister.betsholtz{at}medkem.gu.se

Background— Tumor blood vessels are both structurally and functionally abnormal compared with normal vessels. A limited support of mural cells may contribute to these abnormalities. Here, we characterized mural cell recruitment in 2 mouse tumor models and addressed the question of why tumor vessels fail to recruit a proper coat of mural cells.

Methods and Results— We studied mural cell recruitment to the vasculature of 2 transplantable mouse tumor models, T241 fibrosarcoma and KRIB osteosarcoma. We found that both tumors formed a vessel network with heterogeneous and highly abnormal organization of mural cells. Transplantation of tumors to mice expressing lacZ in mural cells demonstrated that these cells were host-derived. Although tumor vessel endothelium expressed PDGF-B, an embryonic mitogen for mural cells, only very few PDGFRß-positive cells were found to be associated with the developing tumor vasculature, suggesting a limited pool of recruitable mural cells. We tested whether exogenous mural cells could be recruited to tumor vessels by injecting mixtures of T241 tumor cells and embryonic mesenchymal cells isolated from mice expressing lacZ in mural cells. In the tumors that arose, lacZ-positive cells were efficiently recruited to the tumor vessels.

Conclusions— T241 and KRIB tumors show a similar highly abnormal organization of vessel-associated mural cells. T241 tumor vessels seem highly capable of recruiting exogenously added mural cells. The sparse mural cell coat of tumor vessels may result from a limited pool of mural cells available for recruitment.

Key Words: angiogenesis • cells • pericytes • muscle, smooth • growth substances

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