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© The Rockefeller University Press, 0021-9525/1998//1407 $5.00
The Journal of Cell Biology, Volume 141, Number 6, , 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 surface through a glycosyl-phosphatidylinositol anchor. It has recently been shown that the OCI-5/GPC3 gene is mutated in patients with the Simpson-Golabi-Behmel Syndrome (SGBS), an X-linked disorder characterized by pre- and postnatal overgrowth and various visceral and skeletal dysmorphisms. Some of these dysmorphisms could be the result of deficient growth inhibition or apoptosis in certain cell types during development. Here we present evidence indicating that OCI-5/GPC3 induces apoptosis in cell lines derived from mesothelioma (II14) and breast cancer (MCF-7). This induction, however, is cell line specific since it is not observed in NIH 3T3 fibroblasts or HT-29 colorectal tumor cells. We also show that the apoptosis-inducing activity in II14 and MCF-7 cells requires the anchoring of OCI-5/GPC3 to the cell membrane. The glycosaminoglycan chains, on the other hand, are not required. MCF-7 cells can be rescued from OCI-5/GPC3–induced cell death by insulin-like growth factor 2. This factor has been implicated in Beckwith-Wiedemann, an overgrowth syndrome that has many similarities with SGBS. The discovery that OCI-5/GPC3 is able to induce apoptosis in a cell line– specific manner provides an insight into the mechanism that, at least in part, is responsible for the phenotype of SGBS patients.

Abbreviations used in this paper: GAG, glycosaminoglycan; GPI, glycosylphosphatidylinositol; GPC, glypican; HA, hemagglutinin A; IGF2, insulin-like growth factor 2; PARP, poly ADP ribose polymerase; SGBS, Simpson-Golabi-Behmel Syndrome.

Address all correspondence to Dr. Jorge Filmus, Division of Cancer Biology Research, S-218 Research Building, Sunnybrook Health Science Centre, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada. Tel.: (416) 480-6100 ext. 3350. Fax: (416) 480-5703. E-mail: filmus{at}srcl.sunnybrook.utoronto.ca.

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