CD133 positive endothelial progenitor cells contribute to the tumour vasculature in non-small cell lung cancer.
OBJECTIVE
Recent results generated in a mouse model suggest that tumour angiogenesis/vasculogenesis can be initiated and maintained by bone marrow derived endothelial progenitor cells. This present study investigated the distribution and frequency of CD133 positive endothelial progenitor cells in patients with non-small cell lung cancer (NSCLC) (tumour tissue and tumour free lung regions) and healthy controls using fresh frozen specimens. The novel marker CD133 identifies human haemopoetic precursor cells, in addition to human endothelial progenitor cells.


METHODS
Seventy nine lung cancer specimens and 66 adjacent histologically tumour free tissues of the same patient cohort were analysed; 11 postmortem specimens from control patients who did not suffer from malignant disease served as controls. Cryostat sections were stained for CD133, CD31, vascular endothelial growth factor receptor 2 (VEGFR-2; KDR), p53, and the proliferation marker Ki-67, and the correlations were analysed.


RESULTS
Forty three of 63 evaluable tumour specimens had increased numbers of CD133 positive cells and in some cases capillary forming CD133 positive structures were detectable. In addition, 30 of 63 specimens had raised expression of KDR and 29 of 63 had increased MVD. Increased CD133 expression marginally correlated with raised KDR expression but not with p53 and Ki-67.


CONCLUSIONS
A significant increase in CD133 positive cells was documented in patients with NSCLC, suggesting an involvement of endothelial progenitor cells in tumour vasculogenesis and tumour growth in these patients.
Hilbe
W
W
Department of Internal Medicine, University Hospital, Anichstrasse 35, A-6020 Innsbruck, Austria. wolfgang.hilbe@uibk.ac.at
Dirnhofer
S
S
Oberwasserlechner
F
F
Schmid
T
T
Gunsilius
E
E
Hilbe
G
G
Wöll
E
E
Kähler
C M
CM
D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D015703:Antigens, CD; D015415:Biomarkers / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D042783:Endothelial Cells / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology*; D005260:Female; D006023:Glycoproteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000032:analysis; D008175:Lung Neoplasms / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000209:etiology; D010455:Peptides / Q000032:analysis*; D013234:Stem Cells / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis
D000071916:AC133 Antigen; D015703:Antigens, CD; D015415:Biomarkers; D006023:Glycoproteins; D019394:Ki-67 Antigen; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D016159:Tumor Suppressor Protein p53; D040301:Vascular Endothelial Growth Factor Receptor-2