Platelet: transporter of vascular endothelial growth factor.
In animal models, growth of tumors and their metastases is dependent on factors that stimulate vessel formation (angiogenesis). Most clinical studies confirm the importance of angiogenesis for cancer growth in patients. Recent studies on circulating angiogenic factors in patients have focused on serum vascular endothelial growth factor (VEGF) levels in a variety of cancer types. We measured serum VEGF concentrations and blood counts in 27 breast cancer patients during each of 6 cycles of chemotherapy with doxorubicin and cyclophosphamide supported by granulocyte macrophage colony-stimulating factor. Serum VEGF concentrations highly correlated with platelet counts during chemotherapy (r = 0.8; P < 0.01). In particular, during the first treatment cycle, after an initial episode of thrombocytopenia, a strong platelet rebound coincided closely with a serum VEGF peak (r = 0.9; P < 0.01). In addition, plasma VEGF concentrations from 15 other cancer patients and 30 healthy volunteers were 5- to 8-fold lower than their corresponding serum VEGF concentrations (P < 0.001). Activation of platelets increased the VEGF content 8-10 times. These findings demonstrate that VEGF is released by platelets during serum preparation. In this study, we found evidence for VEGF transport by platelets, indicating that serum VEGF concentrations reflect mainly platelet counts rather than tumor burden in cancer patients, as reported earlier. Platelets, known to be important for wound healing, have also been reported to contribute to metastasis formation and tumor growth in animal models. Indeed, tumors can be regarded as never-healing wounds. Our data suggest that platelets may have a stimulating role on angiogenesis-dependent tumor growth through their function as transporters of VEGF.
Verheul
H M
HM
Department of Medical Oncology, University Hospital "Vrije Universiteit," 1007 MB Amsterdam, The Netherlands.
Hoekman
K
K
Luykx-de Bakker
S
S
Eekman
C A
CA
Folman
C C
CC
Broxterman
H J
HJ
Pinedo
H M
HM
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001792:Blood Platelets / Q000502:physiology*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D016228:Endothelial Growth Factors / Q000097:blood*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D008222:Lymphokines / Q000097:blood*; D015539:Platelet Activation; D012016:Reference Values; 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; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide