Identification of CSPG4 as a promising target for translational combinatorial approaches in osteosarcoma.
CSPG4
antibodies
comparative oncology
osteosarcoma
Journal
Therapeutic advances in medical oncology
ISSN: 1758-8340
Titre abrégé: Ther Adv Med Oncol
Pays: England
ID NLM: 101510808
Informations de publication
Date de publication:
2019
2019
Historique:
received:
15
10
2018
accepted:
09
05
2019
entrez:
21
6
2019
pubmed:
21
6
2019
medline:
21
6
2019
Statut:
epublish
Résumé
Osteosarcoma (OSA) is a highly metastatic pediatric bone tumor. Adjuvant chemotherapy and surgical resection represent standard treatments; however, the prognosis is still poor. Effective strategies are urgently needed. Chondroitin sulfate proteoglycan (CSPG)4 is a transmembrane proteoglycan with a low expression in normal tissues but high expression in several solid tumors, where it plays a central tumorigenic role. Therefore, it represents a promising therapeutic target. The high homology between human and canine CSPG4 and the recognized translational power of canine tumors as preclinical models for human malignancies prompted us to evaluate CSPG4 expression and the consequences of its immune-targeting for both human and canine OSA treatment. We analyzed CSPG4 overexpression in human and canine OSA samples and its significance for the survival of OSA patients. We exploited functional CSPG4 is overexpressed in OSA and has possible clinical implications as suggested by an evident correlation between CSPG4 overexpression and a shorter survival for both OSA-affected humans and dogs. The potential of CSPG4 immune-targeting for OSA treatment came from the ability of anti-CSPG4 monoclonal antibodies and sera, derived from human-CSPG4-DNA vaccinated canine patients, to significantly inhibit human and canine CSPG4-positive OSA cell proliferation, migration, and osteospheres generation. Moreover, CSPG4 immune-targeting has been shown to potentiate the effect of doxorubicin. Overall, these results provide the rationale to investigate the CSPG4 immune-targeting as a promising weapon for the treatment of CSPG4-positive OSA canine patients, to be successfully translated to a human setting.
Sections du résumé
BACKGROUND
BACKGROUND
Osteosarcoma (OSA) is a highly metastatic pediatric bone tumor. Adjuvant chemotherapy and surgical resection represent standard treatments; however, the prognosis is still poor. Effective strategies are urgently needed. Chondroitin sulfate proteoglycan (CSPG)4 is a transmembrane proteoglycan with a low expression in normal tissues but high expression in several solid tumors, where it plays a central tumorigenic role. Therefore, it represents a promising therapeutic target. The high homology between human and canine CSPG4 and the recognized translational power of canine tumors as preclinical models for human malignancies prompted us to evaluate CSPG4 expression and the consequences of its immune-targeting for both human and canine OSA treatment.
METHODS
METHODS
We analyzed CSPG4 overexpression in human and canine OSA samples and its significance for the survival of OSA patients. We exploited functional
RESULTS
RESULTS
CSPG4 is overexpressed in OSA and has possible clinical implications as suggested by an evident correlation between CSPG4 overexpression and a shorter survival for both OSA-affected humans and dogs. The potential of CSPG4 immune-targeting for OSA treatment came from the ability of anti-CSPG4 monoclonal antibodies and sera, derived from human-CSPG4-DNA vaccinated canine patients, to significantly inhibit human and canine CSPG4-positive OSA cell proliferation, migration, and osteospheres generation. Moreover, CSPG4 immune-targeting has been shown to potentiate the effect of doxorubicin.
CONCLUSIONS
CONCLUSIONS
Overall, these results provide the rationale to investigate the CSPG4 immune-targeting as a promising weapon for the treatment of CSPG4-positive OSA canine patients, to be successfully translated to a human setting.
Identifiants
pubmed: 31217827
doi: 10.1177/1758835919855491
pii: 10.1177_1758835919855491
pmc: PMC6557023
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1758835919855491Subventions
Organisme : NCI NIH HHS
ID : R03 CA216114
Pays : United States
Déclaration de conflit d'intérêts
Conflict of interest statement: The authors declare that there is no conflict of interests.
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