Co-regulated expression of matrix metalloproteinase-2 and transforming growth factor-beta in melanoma development and progression.
Previous studies have found that matrix metalloproteinase-2 (MMP-2) and transforming growth factor-beta (TGF-beta) can be considered as biomarkers and indices of disease progression in several human cancers. In this study, we investigated the plasma levels of MMP-2 and TGF-beta and their correlation in 49 primary cutaneous melanoma and 10 metastatic melanoma. Plasma MMP-2 and TGF-beta levels in patients with primary melanoma were significantly higher than those of healthy controls. These protein levels were significantly higher in patients with metastatic melanoma. A positive correlation between plasma levels of MMP-2 and TGF-beta in melanoma patients supports the hypothesis that TGF-beta triggers the release of MMP-2. The immunohistochemistry analysis shows that MMP-2 and TGF-beta were highly expressed in tumor tissues as well as in matched plasma samples. This finding suggests that these proteins are released from tumor cells. Overall, our data indicate that MMP-2 and TGF-beta may represent novel diagnostic markers and therapeutic targets in melanoma and the determination of their concentration could be a useful diagnostic and prognostic indicator. TGF-beta, leading the tissue invasion mediated by MMP-2, is a strong promoter of tumor progression. Therefore, reducing or blocking the activity of TGF-beta may represent a promising target in therapeutic strategies for limiting the growth of melanoma.
Dipartimento di Scienze Biomediche, Università di Catania, 95123 Catania, Italy. g.malaponte@unict.it
Grazia
G
Malaponte
Alessandra
A
Zacchia
Ylenia
Y
Bevelacqua
Andrea
A
Marconi
Rosario
R
Perrotta
Maria Clorinda
MC
Mazzarino
Vera
V
Cardile
Franca
F
Stivala
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000378:metabolism*; D008545:Melanoma / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012878:Skin Neoplasms / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000097:blood / Q000378:metabolism*
D014408:Biomarkers, Tumor; D016212:Transforming Growth Factor beta; D020778:Matrix Metalloproteinase 2