We agree with Zavras and colleagues that IGF2R, by sequestering IGF2 without transmitting a mitogenic or survival signal, might be a molecule that serves to restrict proliferation. This view is consistent not only with the studies they cite1,2, but also with other work (for example, REFS 3,4,5). Further translational studies to define the influence of germline variation of IGF2R on cancer risk as well as the impact of variation in the number or function of IGF2Rs on cancer cells or neoplastic behaviour will be of interest.
Zavras, A. I. et al. Insulin-like growth factor II receptor gene-167 genotype increases the risk of oral squamous cell carcinoma in humans. Cancer Res. 63, 296–297 (2003).
Xie, S. & Kang, J. X. Differential expression of the mannose 6-phosphate/insulin-like growth factor-II receptor in human breast cancer cell lines of different invasive potential. Med. Sci. Monit. 8, BR293–BR300 (2002).
Ellis, M. J. et al. Affinity for the insulin-like growth factor-II (IGF-II) receptor inhibits autocrine IGF-II activity in MCF-7 breast cancer cells. Mol. Endocrinol. 10, 286–297 (1996).
Osipo, C., Dorman, S. & Frankfater, A. Loss of insulin-like growth factor II receptor expression promotes growth in cancer by increasing intracellular signaling from both IGF-I and insulin receptors. Exp. Cell Res. 264, 388–396 (2001).
Lee, J. S., Weiss, J., Martin, J. L. & Scott, C. D. Increased expression of the mannose 6-phosphate/insulin-like growth factor-II receptor in breast cancer cells alters tumorigenic properties in vitro and in vivo. Int. J. Cancer 107, 564–570 (2003).