VEGFR2 expressing circulating (progenitor) cell populations in volunteers and cancer patients

Abstract

Circulating cells of several lineages are thought to participate in angiogenesis and tumor growth. Experimental studies in tumor-bearing mice have pointed to the potential importance of VEGF-responding circulating (endothelial) progenitor cells in tumor growth. We have studied circulating CD31- and/or CD34-positive cell populations with a low to moderate VEGFR2 expression in human volunteers and cancer patients. We recognized four cell populations, which were further characterized by their content of major hematopoietic progenitor, monocytic, endothelial and platelet markers. After establishing the test-retest stability of the measurements in nine patients, we determined the frequencies of the various cell populations in a group of 20 volunteers and 14 cancer patients. Two populations were markedly increased in cancer patients. Small CD45(neg)/CD34(bright)/VEGFR2+ cells amounted to 12 and 64 cells/ml (P < 0.0001), respectively, and 246/ml and 578/ml VEGFR2+/CD45(bright) (/CD14+) monocytic cells were present in controls and cancer patients, respectively (P = 0.017). A third population of CD45(dim)/CD34(bright)/VEGFR2(low) cells amounted to 25 and 30 cells/ml (P = 0.38). Unexpectedly, a population of mainly anucleated CD45(low)/CD31(bright)/CD41(bright) cells was present in numbers of 9,076 and 16,697/ml (P = 0.04) in volunteers and cancer patients, which contained a VEGFR2(low) (compared to IgG isotype control) expressing population amounting to 1,142 and 1,642 cells/ml (P = 0.12). This fourth population probably reflects large platelets. The role of the herein identified VEGFR2+ circulating cell populations deserve further investigation in cancer patients treated with VEGF(R)-targeted therapies. Quantification of such cell populations in the blood of tumor patients may be valuable to monitor the efficacy of anti-angiogenic treatment.

CD133+ circulating haematopoietic progenitor cells predict for response to sorafenib plus erlotinib in non-small cell lung cancer patients

“…The cutoff value for CD133 positivity in HPCs was determined based on isotype control and was adjusted for every individual sample. CECs are CD34 bright , which are almost uniformly positive for VEGFR2, but lack both markers CD45 and CD133 as previously defined (Vroling et al, 2007(Vroling et al, , 2009 (Figure 1). …”

“…Blood from SO/ER-treated patients was collected in EDTA tubes and the circulating HPCs and CECs were measured using a fullblood flow cytometric method as previously described (Vroling et al, 2007(Vroling et al, , 2009. (CD133 þ ) HPCs were defined as CD34 bright / CD45 dim (and CD133 þ ) and CECs were defined as CD34 bright / CD45 neg and largely positive for VEGFR2.…”

Vascular Endothelial Growth Factor Receptor 2 Mediates Macrophage Infiltration into Orthotopic Pancreatic Tumors in Mice

“…These data suggest a possible marker (e.g., VEGFR2+ macrophages or circulating monocytes) for identifying pancreatic cancer and a possible marker for the efficacy of antiangiogenic treatment. It is worth noting that higher levels of circulating VEGFR2+ monocytes/macrophages have recently been identified in patients with various advanced solid tumors compared with healthy volunteers (36). The inductive factor in human patients has not been elucidated; however, we show that the cytokine PTN is sufficient to induce VEGFR2 expression in macrophages, a function of PTN that is relevant to the progression of pancreatic cancer.…”

High Levels of Circulating VEGFR2+ Bone Marrow–Derived Progenitor Cells Correlate with Metastatic Disease in Patients with Pediatric Solid Malignancies

“…41). These findings have raised considerable questioning of the reliability of the flow cytometry method for CEC measurement (38,42,43). Recently, in 2007, Strijbos et al argued that cells identified as CECs by flow cytometry in these studies were, in fact, large platelets (42).…”