Matrix metalloproteinases and proangiogenic factors in testicular germ cell tumors.
OBJECTIVE
Testicular cancer is the most frequent solid tumor in young male adults and a disease with elusive pathogenesis. The purpose of this study was to determine the role of matrix metalloproteinases and angiogenic factors in the pathogenesis of testicular germ cell tumors (GCTs).


METHODS
Between 2003 and 2006 we measured the serum levels of matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), vascular endothelial growth factor A (VEGF-A), basic fibroblast growth factor (bFGF), platelet derived growth factor BB (PDGF-BB) and angiopoietin 2 (Ang-2) in 50 patients with testicular GCTs, at baseline, one month after the completion of the second cycle of chemotherapy and one year after the completion of chemotherapy, and in 16 male age-matched controls at baseline.


RESULTS
At baseline, mean TIMP-2 value was lower in patients than controls, mean MMP-2/TIMP-2 ratio was higher in patients than controls and MMP9/TIMP-2 ratio was also higher. Ang-2 value was higher in patients than controls and bFGF value was also higher. Comparisons of the same parameters were also made among the 3 consecutive serum samples of the patients. All parameters normalized after chemotherapy except Ang-2 which remained elevated.


CONCLUSIONS
The present study supports the hypothesis that tumor invasion and angiogenesis play a role in testicular GCTs pathogenesis. Also an interesting hypothesis was formed, concerning the role of elevated levels of Ang-2 found in testicular GCTs patients in the pathogenesis of the increased long term cardiovascular morbidity of these patients. Larger prospective studies are needed to confirm our results.
Diamantopoulos
N
N
3rd Department of Clinical Oncology, Theagenion Cancer Hospital, Thessaloniki, Greece. ndiamantopoulos@yahoo.com
Boutis
A L
AL
Koratzis
I
I
Andreadis
C
C
Galaktidou
G
G
Mouratidou
D
D
Kortsaris
A
A
D000328:Adult; D042501:Angiogenic Proteins / Q000097:blood*; D042702:Angiopoietin-2 / Q000097:blood; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000077214:Becaplermin; D016022:Case-Control Studies; D017024:Chemotherapy, Adjuvant; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D020782:Matrix Metalloproteinases / Q000097:blood*; D009361:Neoplasm Invasiveness; D009373:Neoplasms, Germ Cell and Embryonal / Q000097:blood* / Q000201:enzymology / Q000473:pathology / Q000628:therapy; D009919:Orchiectomy; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D013736:Testicular Neoplasms / Q000097:blood* / Q000201:enzymology / Q000473:pathology / Q000628:therapy; D013997:Time Factors; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D042501:Angiogenic Proteins; D042702:Angiopoietin-2; D000970:Antineoplastic Agents; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D019716:Tissue Inhibitor of Metalloproteinase-2; D000077214:Becaplermin; D020782:Matrix Metalloproteinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9