S100A13 is a new angiogenic marker in human melanoma

Abstract

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 ¼ 0.024), in which it correlated positively with the intensity of VEGF-A staining (P ¼ 0.041) and microvessel density (P ¼ 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) (Po0.001). Furthermore, S100A13 mRNA correlated positively with VEGF-A (P ¼ 0.023), TNM stage (P ¼ 0.05), risk of relapse (P ¼ 0.014) and status at follow-up (P ¼ 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.

Retrospective Proteomic Screening of 100 Breast Cancer Tissues

“…S10AD (S100A13). S10AD has been proposed to play roles in the invasiveness of lung cancer cells [117] and in angiogenesis of human melanoma [118]. In our tissues we found two isoforms of it, one of which ubiquitous, showing a fold increase of almost 2x, and the second, more basic, expressed sporadically.…”

“…As previously reported, the S100AD in our tumor tissues displays two isoforms, the first is ubiquitous with a fold increase of about 2x with respect to the normal tissues (when present), while the second, more basic, was detected sporadically in tumor but it was absent in the normal tissues. The functional role of this S100 protein has been already discussed [117,118].…”

Biomarkers in Malignant Melanoma: Recent Trends and Critical Perspective

“…S100A13, another promising prognostic marker for melanoma, is proposed to be an indicator of the angiogenic switch that facilitates disease progression. Massi and colleagues found expression in dysplastic nevi and in primary and metastatic melanoma with increasingly higher correlation in more aggressive and/or advanced tumors (Breslow thickness and Clark' s level) (64). A proteomics study reported S100A13 to be elevated in cisplatin-resistant melanoma cell lines (65).…”

“…S100A4, also called metastasis-associated protein, is universally overexpressed in a variety of tumor entities and is an independent marker for tumor progression, invasion, metastasis, poor survival, and prognosis (1). S100A4 influences cell motility, inflammation, angiogenesis, and apoptosis due to interaction between tumor cells and their microenvironment (59)(60)(61)(62)(63)(64). However, extracellular S100A4 seems to be of major importance in this context and, therefore, may possibly serve as a blood marker.…”

Overexpression of S100A13 protein is associated with tumor angiogenesis and poor survival in patients with early‐stage non‐small cell lung cancer

“…S100A13 is a small calcium (Ca2+) binding protein belonging to the S100 family and the C‐terminus of the S100A13 protein ends with a special motif, which has also been observed in metastasis‐associated proteins S100A4 and S100A10 . S100A13 is upregulated in human astrocytic gliomas and melanoma, where it correlates with VEGF‐A and FGF‐1 expression and angiogenesis, and is also associated with a more aggressive, invasive phenotype in lung cancer‐derived cell lines . To our knowledge no previous studies have investigated a correlation between S100A13 and angiogenesis and prognosis in surgically resected early‐stage NSCLC.…”