In vivo release of vascular endothelial growth factor from colorectal carcinomas.
The formation of new blood vessels is essential for the growth of malignant tumors and their hematogenic spread. Tumor-induced neoangiogenesis occurs through sprouting of preexisting vessels. An alternative mechanism might be the recruitment of bone marrow-derived endothelial cells, or their precursors, to the tumor site by the release of vascular endothelial growth factor (VEGF) from cancer cells, i.e., tumor-induced postnatal vasculogenesis. To investigate if a significant amount of VEGF is released from malignant tumors in vivo, thus potentially mobilizing endothelial precursor cells (EPC) from the bone marrow, we measured plasma levels of soluble VEGF obtained from tumor-draining mesenteric veins (VEGF-M) during surgery and, simultaneously, in venous blood obtained distant from the tumor (VEGF-P). This analysis was performed in 29 patients with colorectal carcinoma. VEGF-M levels were substantially higher in patients with distant metastases (208 +/- 61 pg/ml) compared to patients with nonmetastatic disease (99 +/- 72 pg/ml, p = 0.003). Also, in patients with aggressive disease, i.e., histologically undifferentiated (G3) tumors, higher levels of VEGF-M were measured than in patients with tumors of lower histologic grading (196 +/- 46 vs. 107 +/- 80 pg/ml, p = 0.01). In conclusion, the release of significant amounts of soluble VEGF in vivo from clinically and/or histologically aggressive tumors might reflect their high angiogenic or vasculogenic potential, probably leading to the recruitment of EPC from the bone marrow.
Division of Hematology and Oncology, University of Innsbruck, Austria. eberhard.gunsilius@uibk.ac.at
Eberhard
E
Gunsilius
Jörg
J
Tschmelitsch
Martin
M
Eberwein
Hubert
H
Schwelberger
Gilbert
G
Spizzo
Christian M
CM
Kähler
Günther
G
Stockhammer
Alois
A
Lang
Andreas L
AL
Petzer
Günther
G
Gastl
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000473:pathology / Q000601:surgery; D016228:Endothelial Growth Factors / Q000097:blood*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008222:Lymphokines / Q000097:blood*; D008297:Male; D008642:Mesenteric Veins / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating; D011379:Prognosis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors