Bone-Marrow Derived Hematopoietic Progenitor Cells and Endothelial Progenitor Cells as Prognostic Indicators for Cancer Relapse

These two cell types, bone marrow derived VEGFR1+ hematopoietic progenitor cell s (HPCs) and VEGFR2+ endothelial progenitor cells (EPCs), have been demonstrated to play important roles in tumor angiogenesis in murine models. Inhibition of these two types of cells blocks the development of metastasis.

The levels of HPCs and EPCs were measured in breast cancer patients to look at the temporal changes in cell number. A surge in the number of HPCs and EPCs was observed in patients prior to progression of disease and was predictive of relapse, while HPC and EPC values decreased in patients that responded to therapy. HPC and EPC numbers did not change in patients with stable disease.

Measuring HPC and EPC levels in the circulation has potential as a clinical biomarker to predict onset of relapse of cancer with significant advantages over existing methods. Current serum-based biomarkers (e.g. CEA and CA15-3) can only predict relapse at a late-stage of the metastatic process by which time the disease has typically become much more aggressive and difficult to treat. The early prediction of metastatic progression allows for the opportunity to intervene with targeted therapy to prevent relapse or further progression. Furthermore, HPC and EPC levels can also be used to predict the response of metastases to therapy, again allowing intervention with alternative therapies before progression of the disease. This method would be beneficial to other types of cancer and these cells may also serve as a therapeutic target for those at high risk of relapse.

Fig 1. Changes in HPC and EPC cell number predicts the onset of relapse

Characteristic pattern of VEGFR1+ and VEGFR2+ hemangiogenic progenitor cells is observed prior to relapse of breast cancer in patients who are without evidence of disease at study entry. An initial surge of VEGFR1+ HPCs is followed by a surge of the VEGFR2+ EPCs prior to overt relapse.