PNAS 2013-12-17

CD13-positive bone marrow-derived myeloid cells promote angiogenesis, tumor growth, and metastasis.

Eleonora Dondossola, Roberto Rangel, Liliana Guzman-Rojas, Elena M Barbu, Hitomi Hosoya, Lisa S St John, Jeffrey J Molldrem, Angelo Corti, Richard L Sidman, Wadih Arap, Renata Pasqualini

Index: Proc. Natl. Acad. Sci. U. S. A. 110(51) , 20717-22, (2013)

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Abstract

Angiogenesis is fundamental to tumorigenesis and an attractive target for therapeutic intervention against cancer. We have recently demonstrated that CD13 (aminopeptidase N) expressed by nonmalignant host cells of unspecified types regulate tumor blood vessel development. Here, we compare CD13 wild-type and null bone marrow-transplanted tumor-bearing mice to show that host CD13(+) bone marrow-derived cells promote cancer progression via their effect on angiogenesis. Furthermore, we have identified CD11b(+)CD13(+) myeloid cells as the immune subpopulation directly regulating tumor blood vessel development. Finally, we show that these cells are specifically localized within the tumor microenvironment and produce proangiogenic soluble factors. Thus, CD11b(+)CD13(+) myeloid cells constitute a population of bone marrow-derived cells that promote tumor progression and metastasis and are potential candidates for the development of targeted antiangiogenic drugs.