Expression and growth dependency of the insulin-like growth factor I receptor in craniopharyngioma cells: a novel therapeutic approach.
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.
Department of Neurosurgery, Institution for Surgical Sciences, Stockholm, Sweden.
Elfar
E
Ulfarsson
Alexandra
A
Karström
Shucheng
S
Yin
Ada
A
Girnita
Daiana
D
Vasilcanu
Marja
M
Thoren
Gunnar
G
Kratz
Jan
J
Hillman
Magnus
M
Axelson
Olle
O
Larsson
Leonard
L
Girnita
D000293:Adolescent; D000328:Adult; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D003397:Craniopharyngioma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007150:Immunohistochemistry; D020128:Inhibitory Concentration 50; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects; D010911:Pituitary Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D011034:Podophyllotoxin / Q000031:analogs & derivatives / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D014407:Tumor Cells, Cultured
C415032:picropodophyllin; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011034:Podophyllotoxin