Rhabdomyosarcomas (RMS) are muscle-derived tumours with a significant incidence in children. RMS cells exhibit a widespread pattern of muscle-specific markers, the detection of which may be useful for discriminating the tumour grading in order to optimize the timing and doses of chemotherapy. By analyzing human RMS specimens and in vitro cell lines, we determined the time window of expression of Caveolins (Cav-1, -2 and -3) and some Cavins family members (i.e. PTRF/Cavin-1 and MURC/Cavin-4). In detail, the simultaneous expression of Cav-1, Cav-2 and PTRF/Cavin-1 defined a signature predictive of immature cells, whereas the expression of Cav-3 and MURC/Cavin-4 was restricted to more differentiated cells. In addition, in immature cells Cav-1 was tyrosine-phosphorylated in a Src-dependent manner, resulting in increased cell proliferation and migration. As a result, the subcutaneous injections into nude mice of RMS cells overexpressing the wild-type Cav-1 form resulted in a significant tumour growth, which was instead prevented by the over-expression of a non-phosphorylatable form of Cav-1. Overall, it can be concluded that Caveolins and Cavins can be useful to identify the degree of cellular differentiation in RMS and that phosphorylation of Cav-1, in particular, plays a key role in tumour aggressiveness.
Caveolins and cavins in muscle-derived tumours.
SORCI, Guglielmo;RIUZZI, Francesca;
2012
Abstract
Rhabdomyosarcomas (RMS) are muscle-derived tumours with a significant incidence in children. RMS cells exhibit a widespread pattern of muscle-specific markers, the detection of which may be useful for discriminating the tumour grading in order to optimize the timing and doses of chemotherapy. By analyzing human RMS specimens and in vitro cell lines, we determined the time window of expression of Caveolins (Cav-1, -2 and -3) and some Cavins family members (i.e. PTRF/Cavin-1 and MURC/Cavin-4). In detail, the simultaneous expression of Cav-1, Cav-2 and PTRF/Cavin-1 defined a signature predictive of immature cells, whereas the expression of Cav-3 and MURC/Cavin-4 was restricted to more differentiated cells. In addition, in immature cells Cav-1 was tyrosine-phosphorylated in a Src-dependent manner, resulting in increased cell proliferation and migration. As a result, the subcutaneous injections into nude mice of RMS cells overexpressing the wild-type Cav-1 form resulted in a significant tumour growth, which was instead prevented by the over-expression of a non-phosphorylatable form of Cav-1. Overall, it can be concluded that Caveolins and Cavins can be useful to identify the degree of cellular differentiation in RMS and that phosphorylation of Cav-1, in particular, plays a key role in tumour aggressiveness.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
