Abstract
BackgroundInsulin-like Growth Factor Receptor-1 (IGF1R) system sustains the genesis of rhabdomyosarcoma through IGF2 autocrine overexpression. While several IGF1R-targeted strategies have been investigated to interphere with rhabdomyosarcoma growth, no attempt to neutralize IGF2 has been reported. We therefore studied the possibility to hamper rhabdomyosarcoma growth with passive and active immune approaches targeting IGF2.MethodsA murine model developing IGF2-overexpressing pelvic rhabdomyosarcoma, along with IGF2-independent salivary carcinoma, was used to investigate the efficacy and specificity of passive anti-IGFs antibody treatment. Active vaccinations with electroporated DNA plasmids encoding murine or human IGF2 were performed to elicit autochthonous anti-IGF2 antibodies. Vaccinated mice received the intravenous injection of rhabdomyosarcoma cells to study the effects of anti-IGF2 antibodies against developing metastases.ResultsPassive administration of antibodies neutralizing IGFs delayed the onset of IGF2-overexpressing rhabdomyosarcoma but not of IGF2-independent salivary carcinoma. A DNA vaccine against murine IGF2 did not elicit antibodies, even when combined with Treg-depletion, while a DNA vaccine encoding the human IGF2 gene elicited antibodies crossreacting with murine IGF2. Mice with anti-IGF2 antibodies were partially protected against the metastatic growth of IGF2-addicted rhabdomyosarcoma cells.ConclusionsImmune targeting of autocrine IGF2 inhibited rhabdomyosarcoma genesis and metastatic growth.
Highlights
Insulin-like Growth Factor Receptor-1 (IGF1R) system sustains the genesis of rhabdomyosarcoma through Insulin-like Growth Factor-2 (IGF2) autocrine overexpression
Rhabdomyosarcoma is characterized by the overexpression of Insulin-like Growth Factor-2 (IGF2) that sustains growth in an autocrine way, interacting with the Insulin-like Growth Factor Receptor-1 (IGF1R) [1,2,3,4]
We previously found that rhabdomyosarcomas, but not salivary gland carcinomas, overexpressed IGF2 concomitant to membrane Insulin-like Growth Factor receptor-1 (IGF1R), suggesting that, like the human counterpart, experimental rhabdomyosarcoma could harbor an autocrine Insulin-like Growth Factors (IGFs) circuit [19]
Summary
Insulin-like Growth Factor Receptor-1 (IGF1R) system sustains the genesis of rhabdomyosarcoma through IGF2 autocrine overexpression. While several IGF1R-targeted strategies have been investigated to interphere with rhabdomyosarcoma growth, no attempt to neutralize IGF2 has been reported. We studied the possibility to hamper rhabdomyosarcoma growth with passive and active immune approaches targeting IGF2. Rhabdomyosarcoma is characterized by the overexpression of Insulin-like Growth Factor-2 (IGF2) that sustains growth in an autocrine way, interacting with the Insulin-like Growth Factor Receptor-1 (IGF1R) [1,2,3,4]. IGF2-targeted siRNA cause a decreased in vitro growth of Several therapeutic strategies targeting IGF1R are reported in the literature [7]. Passive administration of anti-IGF1R antibodies can block the autocrine system, inhibiting rhabdomyosarcoma tumor growth [8, 9]. An attempt to obtain an active immune response against IGF1R has been reported in a mammary cancer model [12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
