Antitumorigenic effects of a mutant Heparin Affin Regulatory Peptide on the U87 MG glioblastoma cell line

CÉLIA DOS SANTOS; RACHA KARAKY; DOMINIQUE RENOIR; YAMINA HAMMA-KOURBALI; JOSÉ COURTY; JEAN DELBÉ

Otro; 3rd European Course of in vivo Preclinical Assays in Cancer Therapy; 2010

Glioblastoma is themost common primary brain tumor in human adults. Since existing treatments arenot effective enough, novel therapeutic targets must be sought. Theheparin-binding growth factor (HARP), also known as pleiotrophin (PTN), couldpotentially represent such a target. We have previously shown that a mutantprotein, HARP∆111-136, which lacks HARP?s C-terminal 26 amino-acids, acts as adominant negative HARP effector by heterodimerizing with the wild-type growthfactor. The aim of this study was to evaluate the potential inhibitory activityof HARP∆111-136 on the U87 MG human glioblastoma cell line. By overexpressingthe truncated form of HARP in stably established clones of U87 MG cells, weobserved an inhibition of proliferation under both anchorage-dependent and anchorage-independentconditions. We confirmed these results in an in vivo subcutaneous tumorxenograft model. In addition, we found that HARP∆111-136 inhibited cell proliferationin a paracrine manner. Interestingly, HARP∆111-136 was also able to abolishangiogenic activity in HUVEC proliferation and in a Matrigel plug assay. Theseresults demonstrate that considering its anti-proliferative and angiostaticeffects, HARP∆111-136 could be of great interest when used in conjunction withstandard treatments.