A molecular mechanism by which cancer cells may elude the immune surveillance involves the increased expression of the Fas ligand (FasL), able to induce apoptosis of Fas-expressing T cell infiltrates. Up to date, few and contradictory studies have investigated the expression of the Fas/FasL system in human testicular germ cell tumors (TGCT). In the present study, we analyzed the expression of FasL and its cognate receptor Fas in 13 seminomas and 6 normal testicular tissues obtained following orchiectomy. Tissue samples have been processed to prepare either total RNA or protein extracts or fixed and embedded in paraffin for IHC experiments following standard procedures. Quantitative RT-PCR experiments demonstrated in testicular cancers a significant (p<0.01) increase of the FasL mRNA expression of 21.1±5.4 fold, with respect to normal tissues. On the contrary, in the same cancer tissues the levels of Fas mRNA were significantly (p<0.01) reduced to 0.29±0.16 fold, compared to normal tissues. In order to confirm these observations, western blot experiments have been performed using protein extracts from 3 normal testicular tissues and 5 seminomas. The results showed a significant increase of FasL and a concomitant decrease of Fas proteins in testicular cancer tissues, with respect to normal testis. These findings were further confirmed by IHC experiments showing a significant increase of FasL and a decrease of Fas immunoreactivity in cancer cells with respect to control tissues. Finally, since data reported in literature suggest that serum level of soluble FasL (sFasL) could represents a tumor marker for patients affected by TGCT, we have measured its level in the serum of 20 patients affected by seminomas and 10 healthy males. No differences in the serum level of sFasL could be observed between healthy males and patients affected by TGCT. In conclusion, our data demonstrated that: 1) the progression of TGCT is associated with an increased expression of FasL and a concomitant reduction of Fas, providing molecular evidence for the ability of TGCT to elude the immune surveillance; 2) serum level of sFasL does not represent a tumor marker for patients affected by TGCT.
EXPRESSION OF FAS AND FAS LIGAND IN TESTICULAR GERM CELL TUMORS / Baldini, Enke; Marchioni, E; Di Benedetto, A; Giovannetti, G; Coletta, I; DI FIORE, Agnese; Pace, D; Petrangeli, Elisa; Sentinelli, S; Perrone Donnorso, R; Reale, Mg; Mottolese, M; Gandini, Loredana; Ulisse, Salvatore; Lenzi, Andrea; D’Armiento, M.. - In: JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION. SUPPLEMENT. - ISSN 1121-1369. - STAMPA. - 30, Suppl. to No. 4:(2007), pp. 117-117. (Intervento presentato al convegno XXXII National Congress of the Italian Society of Endocrinology tenutosi a Verona, Italy nel 13-16 June 2007).
EXPRESSION OF FAS AND FAS LIGAND IN TESTICULAR GERM CELL TUMORS
BALDINI, ENKE;DI FIORE, AGNESE;PETRANGELI, Elisa;GANDINI, Loredana;ULISSE, SALVATORE;LENZI, Andrea;
2007
Abstract
A molecular mechanism by which cancer cells may elude the immune surveillance involves the increased expression of the Fas ligand (FasL), able to induce apoptosis of Fas-expressing T cell infiltrates. Up to date, few and contradictory studies have investigated the expression of the Fas/FasL system in human testicular germ cell tumors (TGCT). In the present study, we analyzed the expression of FasL and its cognate receptor Fas in 13 seminomas and 6 normal testicular tissues obtained following orchiectomy. Tissue samples have been processed to prepare either total RNA or protein extracts or fixed and embedded in paraffin for IHC experiments following standard procedures. Quantitative RT-PCR experiments demonstrated in testicular cancers a significant (p<0.01) increase of the FasL mRNA expression of 21.1±5.4 fold, with respect to normal tissues. On the contrary, in the same cancer tissues the levels of Fas mRNA were significantly (p<0.01) reduced to 0.29±0.16 fold, compared to normal tissues. In order to confirm these observations, western blot experiments have been performed using protein extracts from 3 normal testicular tissues and 5 seminomas. The results showed a significant increase of FasL and a concomitant decrease of Fas proteins in testicular cancer tissues, with respect to normal testis. These findings were further confirmed by IHC experiments showing a significant increase of FasL and a decrease of Fas immunoreactivity in cancer cells with respect to control tissues. Finally, since data reported in literature suggest that serum level of soluble FasL (sFasL) could represents a tumor marker for patients affected by TGCT, we have measured its level in the serum of 20 patients affected by seminomas and 10 healthy males. No differences in the serum level of sFasL could be observed between healthy males and patients affected by TGCT. In conclusion, our data demonstrated that: 1) the progression of TGCT is associated with an increased expression of FasL and a concomitant reduction of Fas, providing molecular evidence for the ability of TGCT to elude the immune surveillance; 2) serum level of sFasL does not represent a tumor marker for patients affected by TGCT.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
