OCI-5/GPC3, a Glypican Encoded by a Gene That Is Mutated in the Simpson-Golabi-Behmel Overgrowth Syndrome, Induces Apoptosis in a Cell Line-specific Manner

doi:10.1083/jcb.141.6.1407

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J. Cell Biol., Volume 141, Number 6, June 15, 1998 1407-1414

OCI-5/GPC3, a Glypican Encoded by a Gene That Is Mutated in the Simpson-Golabi-Behmel Overgrowth Syndrome, Induces Apoptosis in a Cell Line-specific Manner

Alfonso Dueñas Gonzalez,^* Mitsunori Kaya,^* Wen Shi,^* Howard Song,^* Joseph R. Testa,^§ Linda Z. Penn, and Jorge Filmus^*

^* Division of Cancer Biology Research, Sunnybrook Health Science Centre, Toronto, Ontario M4N 3M5, Canada; Department of Medical Biophysics, University of Toronto, Ontario M5G 2M9, Canada; ^§ Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111; and Ontario Cancer Institute, Ontario M5G 2M9, Canada

OCI-5/GPC3 is a member of the glypican family. Glypicans are heparan sulfate proteoglycans that are bound to the cell surfacethrough a glycosyl-phosphatidylinositol anchor. It has recentlybeen shown that the OCI-5/GPC3 gene is mutated in patients withthe Simpson-Golabi-Behmel Syndrome (SGBS), an X-linked disordercharacterized by pre- and postnatal overgrowth and various visceraland skeletal dysmorphisms. Some of these dysmorphisms could bethe result of deficient growth inhibition or apoptosis in certaincell types during development. Here we present evidence indicatingthat OCI-5/GPC3 induces apoptosis in cell lines derived from mesothelioma(II14) and breast cancer (MCF-7). This induction, however, iscell line specific since it is not observed in NIH 3T3 fibroblastsor HT-29 colorectal tumor cells. We also show that the apoptosis-inducingactivity in II14 and MCF-7 cells requires the anchoring of OCI-5/GPC3to the cell membrane. The glycosaminoglycan chains, on the otherhand, are not required. MCF-7 cells can be rescued from OCI-5/GPC3-inducedcell death by insulin-like growth factor 2. This factor has beenimplicated in Beckwith-Wiedemann, an overgrowth syndrome thathas many similarities with SGBS. The discovery that OCI-5/GPC3is able to induce apoptosis in a cell line- specific manner providesan insight into the mechanism that, at least in part, is responsiblefor the phenotype of SGBS patients.

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