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Expression and Growth Dependency of the Insulin-Like Growth Factor I Receptor in Craniopharyngioma Cells: A Novel Therapeutic Approach

Authors' Affiliations: Departments of ¹ Neurosurgery, ² Endocrinology and Diabetology, and ³ Clinical Chemistry, ⁴ Institution for Surgical Sciences, ⁵ Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska University Hospital, Stockholm, Sweden; Departments of ⁶ Plastic Surgery, and ⁷ Neurosurgery, University Hospital, Linköping, Sweden

Requests for reprints: Department of Oncology and Pathology, Cancer Center Karolinska, R08:04, Karolinska University Hospital, Stockholm 17176, Sweden. Phone: 46-8-5177-5242; Fax: 46-8-321047; E-mail: Leonard.Girnita{at}cck.ki.se.

Craniopharyngioma is a rare benign intracranial epithelial tumor that, however, often recurs and sometimes kills the affected patients, one-third of which are children. In many cases, the patients acquire growth hormone deficiency and postoperatively need substitution. Generally, growth hormone promotes local release of insulin-like growth factor I (IGF-I), which in turn activates the IGF-I receptor (IGF-IR) if present. Together, these circumstances raise the question whether IGF-IR may be involved in craniopharyngioma growth. To address this issue, we analyzed phenotypically well-characterized primary low-passage craniopharyngioma cell lines from nine different patients for IGF-IR expression and IGF-I dependency. Two of the cell lines showed no/very low expression of the receptor and was independent on IGF-I, whereas five cell lines exhibited a strong expression and was clearly contingent on IGF-I. The two remaining cell lines had low receptor expression and IGF-I dependency. Upon treatment with an IGF-IR inhibitor, cells with high IGF-IR expression responded promptly with decreased Akt phosphorylation followed by growth arrest. These responses were not seen in cells with no/very low receptor expression. Growth of cell lines with low IGF-IR expression was only slightly affected by IGF-IR inhibition. Taken together, our data suggest that IGF-IR may be involved in the growth of a subset of craniopharyngiomas and points to the possibility of the involvement of IGF-IR inhibitors as a treatment modality to obtain complete tumor-free conditions before growth hormone substitution.

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