Chemokines direct endothelial progenitors into tumor neovessels

Abstract

Tumor neovasculature substantially derives from sprouting of existing vessels, whereas the functional contribution of bone marrow-derived progenitors to neovessels remains controversial. We used transgenic mouse models of multistep carcinogenesis to monitor incorporation of bone marrow-derived cells into the neovasculature and to elucidate mechanisms of endothelial precursor cell (EPC) recruitment into the tumor microenvironment. We unequivocally demonstrate integration of bone marrow cells into the tumor vasculature as a late event in carcinogenesis that temporally correlates with VEGF release by the tumor and mobilization of circulating EPC in the periphery. Moreover, we demonstrate a chemokine-dependent mechanism of EPC homing into tumor, whereby neovessels of late-stage tumors release a battery of CC chemokines, which direct CCR2 ؉ and CCR5 ؉ progenitors into the vasculature. Thus, we show that tumor vessels promote their own growth and development in a self-amplifying fashion.cancer ͉ neovascularization

Endothelial progenitor cells for cancer gene therapy

“…Other studies also highlighted the important contribution of EPCs during the early phase of tumor neovascularization. 19,20 Treatment of tumor-bearing mice with vascular disrupting agents recruited EPCs to the tumors. 21 In patients with hepatocellular carcinoma, CD 133 + EPCs incorporated into tumor vessels.…”

Role of endothelial progenitor cells in breast cancer angiogenesis: from fundamental research to clinical ramifications

“…In contrast, the concentration of SDF-1a within the tumor is increased in response to VEGF, and the progenitor cells are subsequently trapped in the tumor [36]. Other chemokines, including CCL2 and CCL5, were also reported to be produced by tumor cells to attract the progenitor cells from the circulation [43]. Suriano et al [31] have reported that bone marrow-derived EPC initiate the neovascularization of TG1-1 mammary cells implanted in the inguinal mammary gland of Tie-2 GFP transgenic mice.…”

Potential of tumour cells for delivering oncolytic viruses

“…A fascinating possibility would be, prior to OV/carrier treatment, to begin by injecting cells known to respond to chemotactic molecules and growth factors produced by tumours (for example mesenchymal, endothelial or bone marrow progenitors). [48][49][50][51][52] The natural or built-in chemoresistance of these cells should enhance their participation in tumour vessel formation in patients under chemotherapy. 53 By administering such Trojan horses at the time of primary tumour resection, which often correlates with the release of metastatic growth from anti-angiogenic restrictions, 54 it should be possible to promote their infiltration into the pre-metastatic niche.…”