Angiogenic growth factors in tissue homogenates of HNSCC: expression pattern, prognostic relevance, and interrelationships.
Head and neck squamous cell carcinoma has still a poor prognosis. Since angiogenesis is crucial for tumor growth, a better understanding of the potential clinical relevance as well as the interactions between the numerous proangiogenic growth factors is essential to develop improved therapeutic strategies in these tumors. Expression levels of eight growth factors known to induce angiogenesis (HGF, bFGF, VEGF-A, VEGF-D, PDGF-AB, PDGF-BB, G-CSF, and GM-CSF) were quantitatively measured by ELISA in homogenates of 41 head and neck squamous cell carcinomas. In addition, microvessel density and protein localization of growth factors were assessed by immunohistochemistry. Statistical analysis was performed to assess interrelationships between growth factors analyzed and to correlate protein levels with patient outcome. In 90% of the tissues at least 4/8 growth factors analyzed were detectable. Highest amounts and most frequent expression were found for HGF, bFGF and VEGF-A while PDGF-AB and PDGF-BB were present in two-thirds and G-CSF and GM-CSF in approximately half of the cases. Although there was no significant relation to microvessel density, we identified significant associations for bFGF with HGF and G-CSF as well as of PDGF-AB with those of VEGF-A and PDGF-BB. For the first time we demonstrate that expression levels of HGF as well as that of bFGF and G-CSF in head and neck squamous tumors are negative prognostic factors for patient survival. Our data indicate a network of interrelated and prognostically relevant growth factors in these tumors that have to be taken into consideration when planning an antiangiogenic and antitumor therapy.
Montag
Michael
M
Department of Otorhinolaryngology, Head and Neck Surgery, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
Dyckhoff
Gerhard
G
Lohr
Jennifer
J
Helmke
Burkhard M
BM
Herrmann
Eva
E
Plinkert
Peter K
PK
Herold-Mende
Christel
C
D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000077214:Becaplermin; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000378:metabolism* / Q000401:mortality*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000401:mortality*; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011379:Prognosis; D020574:Proto-Oncogene Proteins c-sis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D042643:Vascular Endothelial Growth Factor D / Q000378:metabolism
D043925:Angiogenesis Inducing Agents; D036341:Intercellular Signaling Peptides and Proteins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D042461:Vascular Endothelial Growth Factor A; D042643:Vascular Endothelial Growth Factor D; C095477:platelet-derived growth factor AB; D000077214:Becaplermin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor