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Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)
Published on: December 19, 2019
Enhanced in vivo thromboxane biosynthesis in melanoma compared with basal cell carcinoma skin cancers
Giovanna Petrucci1, Alessandro Di Stefani2,3, Alessandro Rizzi4
1Facoltà Dipartimentale di Medicina e Chirurgia, Università UniCamillus, Saint Camillus International University of Health Sciences, Rome, Italy.
Background:
Activated platelets have been shown to promote tumorigenesis of several solid, largely gastrointestinal, tumours through the biosynthesis of cyclooxygenase-1-dependent thromboxane A2 (TXA2). The biosynthesis of the proinflammatory prostaglandin E2 (PGE2) has also been implicated in the progression of those solid tumours. Preclinical data suggest that platelet activation and PGE2 may contribute to melanoma progression, but clinical evidence is limited.
Objectives:
To investigate whether melanoma is associated with increased in vivo platelet activation and PGE2 biosynthesis, as assessed by urinary 11-dehydro-thromboxane B2 (11-dehydro-TXB2) and PGE2 metabolite (PGEM) levels, respectively, as compared with basal cell carcinoma (BCC) and healthy control samples; we also explored their potential relevance as biomarkers of melanoma progression.
Methods:
We measured urinary 11-dehydro-TXB2, a major TXA2 metabolite and a biomarker of in vivo platelet activation, as well as PGEM, in patients with melanoma and in patients with BCC, using age- and sex-matched healthy participants as controls. Thirty patients with stage 1-3 melanoma [mean (SD) age 57 (15) years; 21 men] and 24 patients with BCC [mean (SD) age 60 (12) years; 11 men] voluntarily participated in the study; 38 age- and sex-matched healthy individuals [mean (SD) age 56 (17) years; 26 men] from previously published studies by our group were included as controls.
Results:
Urinary 11-dehydro-TXB2 was higher in patients with melanoma [median 1284 pg mg-1 creatinine; interquartile range (IQR) 892-1784] vs. those with BCC (median 583 pg mg-1 creatinine; IQR 393-721) and healthy control participants (median 669 pg mg-1 creatinine; IQR 411-1184) (P < 0.001). Urinary 11-dehydro-TXB2 was comparable between patients with BCC and healthy control participants. We also studied six patients with stage 4 melanoma who showed the highest urinary 11-dehydro-TXB2 levels [1898.0 (IQR 1769.3-2622.1); P = 0.005 vs. all other groups]. PGEM levels did not differ among groups.
Conclusions:
Melanoma, unlike BCC, is associated with increased biosynthesis of biomarkers of activated platelets. Urinary 11-dehydro-TXB2 may be tested as a prognostic biomarker for melanoma progression. Moreover, whether inhibition of platelet activation may be an adjuvant chemopreventive strategy warrants further investigation.
