Role of endothelial progenitor cells in cancer progression.
Tumor-associated neovasculature is a critical therapeutic target; however, despite significant progress made in the clinical efficacy of anti-vessel drugs, the effect of these agents remains transient: over time, most patients develop resistance, which inevitably leads to tumor progression. To develop more effective treatments, it is imperative that we better understand the mechanisms involved in tumor vessel formation, how they participate to the tumor progression and metastasis, and the best way to target them. Several mechanisms contribute to the formation of tumor-associated vasculature: i) neoangiogenesis; ii) vascular co-option; iii) mosaicism; iv) vasculogenic mimicry, and v) postnatal vasculogenesis. These mechanisms can also play a role in the development of resistance to anti-angiogenic drugs, and could serve as targets for designing new anti-vascular molecules to treat solid as well as hematological malignancies. Bone marrow-derived endothelial progenitor cell (EPC)-mediated vasculogenesis represents an important new target, especially at the early stage of tumor growth (when EPCs are critical for promoting the "angiogenic switch"), and during metastasis, when EPCs promote the transition from micro- to macro-metastases. In hematologic malignancies, the EPC population could be related to the neoplastic clone, and both may share a common ontogeny. Thus, characterization of tumor-associated EPCs in blood cancers may provide clues for more specific anti-vascular therapy that has both direct and indirect anti-tumor effects. Here, we review the role of vasculogenesis, mediated by bone marrow-derived EPCs, in the progression of cancer, with a particular focus on the role of these cells in promoting progression of hematological malignancies.
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; University of Bari Medical School, Department of Biomedical Sciences and Human Oncology (DIMO), Section of Internal Medicine and Clinical Oncology, Bari, Italy.
Michele
M
Moschetta
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Yuji
Y
Mishima
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Ilyas
I
Sahin
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Salomon
S
Manier
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Siobhan
S
Glavey
University of Bari Medical School, Department of Biomedical Sciences and Human Oncology (DIMO), Section of Internal Medicine and Clinical Oncology, Bari, Italy.
Angelo
A
Vacca
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Aldo M
AM
Roccaro
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. Electronic address: irene_ghobrial@dfci.harvard.edu.
Irene M
IM
Ghobrial
D000818:Animals; D018450:Disease Progression; D042783:Endothelial Cells / Q000473:pathology*; D019337:Hematologic Neoplasms / Q000473:pathology; D006801:Humans; D009369:Neoplasms / Q000098:blood supply* / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology*; D013234:Stem Cells / Q000473:pathology*
Cancers; Endothelial progenitor cells; Hematological malignancies; Vasculogenesis