S100A13 is a new angiogenic marker in human melanoma.
Angiogenesis is critical in melanoma progression and metastasis and relies on the synthesis and release of proangiogenic molecules such as vascular endothelial growth factor (VEGF)-A and fibroblast growth factors (FGFs). S100A13 is a small calcium-binding protein that facilitates the release of FGF-1, the prototype of the FGF family. S100A13 is upregulated in astrocytic gliomas, in which it correlates with VEGF-A expression, microvessel density and tumor grading, and promotes a more aggressive, invasive phenotype in lung cancer-derived cell lines. To investigate the involvement of S100A13 in human cutaneous melanoma, we analyzed a series of 87 cutaneous melanocytic lesions: 14 common acquired melanocytic nevi, 14 atypical, so-called 'dysplastic' nevi, 45 melanomas (17 radial growth phase and 28 vertical growth phase) and 14 melanoma metastases. Main clinical and pathological features, including histotype, Breslow thickness, Clark's level and outcome were recorded. Microvessel density was determined with CD105/endoglin staining. Semiquantitative determination of S100A13, FGF-1 and VEGF-A protein expression was obtained by immunostaining. Quantification of S100A13 mRNA was achieved by real-time PCR. We found that S100A13 was expressed in melanocytic lesions; compared with benign nevi, S100A13 protein expression was significantly upregulated in melanomas (P=0.024), in which it correlated positively with the intensity of VEGF-A staining (P=0.041) and microvessel density (P=0.007). The level of expression of S100A13 mRNA also significantly increased with progression of disease, from radial growth phase (0.7+/-0.7) to vertical growth phase (3.6+/-3.1) to metastases (7.0+/-7.0) (P<0.001). Furthermore, S100A13 mRNA correlated positively with VEGF-A (P=0.023), TNM stage (P=0.05), risk of relapse (P=0.014) and status at follow-up (P=0.024). In conclusion, S100A13 is expressed in melanocytic lesions when the angiogenic switch occurs and it may cooperate with VEGF-A in supporting the formation of new blood vessels, favoring the shift from radial to vertical tumor growth. Therefore, S100A13 may represent a new angiogenic and prognostic marker in melanoma.
Massi
Daniela
D
Division of Pathological Anatomy, Department of Critical Care Medicine and Surgery, University of Florence, Florence, Italy.
Landriscina
Matteo
M
Piscazzi
Annamaria
A
Cosci
Elena
E
Kirov
Alek
A
Paglierani
Milena
M
Di Serio
Claudia
C
Mourmouras
Vasileios
V
Fumagalli
Stefano
S
Biagioli
Maurizio
M
Prudovsky
Igor
I
Miracco
Clelia
C
Santucci
Marco
M
Marchionni
Niccolò
N
Tarantini
Francesca
F
D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002196:Capillaries / Q000737:chemistry* / Q000473:pathology; D000071063:Endoglin; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000098:blood supply* / Q000737:chemistry* / Q000556:secondary; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009418:S100 Proteins / Q000032:analysis* / Q000235:genetics; D012878:Skin Neoplasms / Q000098:blood supply* / Q000737:chemistry* / Q000473:pathology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D015703:Antigens, CD; D014408:Biomarkers, Tumor; C064206:ENG protein, human; D000071063:Endoglin; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D009418:S100 Proteins; C511523:S100A13 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016220:Fibroblast Growth Factor 1