Circulating endothelial cells and progenitors: potential biomarkers of renal cell carcinoma.
OBJECTIVE
To compare the levels of circulating endothelial cells (CECs) and progenitors (CEPs) between tumour-bearing mice and healthy controls, in human renal cell carcinoma (RCC) xenograft models. The secondary objective was to correlate CEC and CEP levels with tumour variables such as tumour volume, weight and vascularity, indicators of disease severity.


METHODS
Two human RCC xenograft models were used. Tumour cells were inoculated either subcutaneously or beneath the renal subcapsule (orthotopic). Tumour dimensions were recorded and blood samples were taken throughout the experiment, as well as at the end of the experiment, upon which tumours were excised and prepared for histological examination. All blood samples were analysed by flow cytometry.


RESULTS
CEC and CEP levels were significantly elevated in tumour-bearing mice compared with healthy controls. In particular, there was a divergence in CEC levels between RCC-bearing mice and controls during early phases in disease, whereas CEP levels were only elevated towards the end. Additionally, CEC levels correlated with tumour variables such as tumour volume, when tumour volume was <200 mm³ and with tumour vascularity in certain models. CEP levels did not correlate significantly with most tumour variables examined.


CONCLUSIONS
In human RCC xenograft models, CEC levels showed promise as an adjuvant biomarker in evaluating disease burden. RESULTS from correlating CEC levels with tumour variables such as tumour volume, weight and vascularity suggested that CEC levels were a better prognostic indicator during early phases of tumour growth. CEP levels were elevated in tumour-bearing mice compared with controls; however, enumerated numbers were small and require further validation in future studies.
Namdarian
Benjamin
B
Department of Urology, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia. bnamdarian@gmail.com
Tan
Kevin V S
KV
Fankhauser
Matthew J
MJ
Nguyen
Thanh T
TT
Corcoran
Niall M
NM
Costello
Anthony J
AJ
Hovens
Christopher M
CM
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000473:pathology*; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D007680:Kidney Neoplasms / Q000098:blood supply / Q000473:pathology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D009389:Neovascularization, Pathologic; D011379:Prognosis; D013234:Stem Cells / Q000473:pathology*; D014183:Transplantation, Heterologous