Adrenomedullin (AM) is a multifunctional peptide vasodilator that transduces
its effects through calcitonin receptor-like receptor/receptor activity-modifying
protein-2 and -3 (CLR/RAMP2 and CLR/RAMP3). In this study, real-time
quantitative reverse transcription demonstrated a significant expression of AM
mRNA in tumor samples from colorectal cancer (CRC) patients in clinical
stage II, III, and IV when compared with normal colorectal tissue. AM, CLR,
RAMP2, and RAMP3 proteins were immunohistochemically localized in the
carcinomatous epithelial compartment of CRC tissue. Tissue microarray analysis
revealed a clear increase of AM, CLR, RAMP2, and RAMP3 staining in
lymph node and distant metastasis when compared with primary tumors. The
human colon carcinoma cells HT-29 expressed and secreted AM into the culture
medium with a significant increase under hypoxia. Treatment of HT-29
cells with synthetic AM stimulated cell proliferation and invasion in vitro.
Incubation with anti-AM antibody (aAM), anti-AM receptors antibodies
(aAMR), or AM antagonist AM22–52 inhibited significantly basal levels of proliferation
of HT-29 cells, suggesting that AM may function as an autocrine
growth factor for CRC cells. Treatment with aAM significantly suppressed the
growth of HT-29 tumor xenografts in vivo. Histological examination of aAMtreated
tumors showed evidence of disruption of tumor vascularity with
decreased microvessel density, depletion of endothelial cells and pericytes, and
increased tumor cell apoptosis. These findings highlight the potential importance
of AM and its receptors in the progression of CRC and support the
conclusion that aAM treatment inhibits tumor growth by suppression of
angiogenesis and tumor growth, suggesting that AM may be a useful therapeutic
target
| Référence | 2987 |
| Année | 2013 |
| Type | Article |
| Lien document | |
| Lien externe | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639658/ |
| Disciplines associées | Laboratoire |
| Auteur | Nouguer ede E |
| Auteurs associés | Berenguer C, Garcia S, Bennani B, Delfino C, Nanni I, Dahan L, Gasmi M, Seitz J-F, Martin PM, Ouafik L |
| Discipline | Autres |
| Revue | Cancer Medicine |
| Référence Revue | 2(2): 196–207 |
