Title:Somatostatin, Somatostatin Analogs and Somatostatin Receptor Dynamics in the Biology of Cancer Progression
Volume: 13
Issue: 4
Author(s): M. Ruscica, M. Arvigo, L. Steffani, D. Ferone and P. Magni
Affiliation:
Keywords:
Angiogenesis in cancer, cancer cell proliferation, metastatization, somatostatin, somatostatin analogs in
cancer, somatostatin receptors in cancer
Abstract: The pharmacological effects (i.e., inhibition of endocrine secretion and cell proliferation) mediated by
the hormone somatostatin (SRIF) are derived from its universal high-affinity binding to five different G proteincoupled
receptors (GPCRs), named sst1-5. However, SRIF has a half-life of less than 3 min, whereas the
available mono- and bi-specific SRIF preferential analogs show prolonged half-life and increased potency.
These compounds may control tumor development, cell proliferation and metastatization by direct actions,
including cell division arrest in G0/G1 phase (i.e., induction of cyclin-dependent kinase inhibitor p27kip1 or
p21Cip1), induction of apoptosis (i.e., induction of p53 and Bax) and suppression of cell invasion. Along with
these direct actions on the biology of cancer progression, in vivo SRIF analogs may also regulate tumor growth
through indirect actions, by suppressing the secretion of growth-promoting hormones and growth factors and
angiogenesis. Interestingly, when ssts are co-expressed, they may interact forming homo- or heterodimers,
also with other GPCRs such as type 2 dopamine receptor and the μ-opioid receptor 1, altering their original
pharmacological and functional properties. Dimers can be not only constitutive, but perhaps also ligandpromoted:
hence, compounds with high affinity for different ssts isoforms may be used to achieve effects
elicited by specific dimers. Future developments in the knowledge of ssts dynamics upon SRIF and SRIF
analogs binding in neoplastic tissues may allow the full elucidation of the pathophysiological role of this system
and the exploitation of the therapeutic potential of its modulation.
