During the late phase of metastasis, additional alterations in haemostasis (increased PAI-1 and vWF), as well as a rise in ADM and substantial fall in ADN concentration, were observed.
We used siRNA gene silencing, in BGC-823 gastric cancer cell lines, to target adrenomedullin genes, and found that increased adrenomedullin expression results in the proliferation of tumor cells, tumor invasion, and metastasis.
ADM may induce microvessel proliferation and partially decrease hypoxia in solid tumors, thus contributing to the proliferation of tumor cells, as well as tumor invasion and metastasis.
Gene expression analysis showed that several genes involved in tumor development and metastasis (EGR1, COX2, MALAT1, AKAP12, ADM) were similarly induced in CSC and cisplatin-resistant H460 cells, in agreement with a close similarity between these two cell populations.
ADM may be involved in micro-vessel proliferation and partially in the release of hypoxia in solid tumors, contributing to the proliferation of tumor cells as well as local tumor invasion and metastasis.
We found that patients with high AM expression showed a higher incidence of metastasis, larger residual size of tumors after cytoreduction and shorter disease-free and overall survival time.
Furthermore, increasing adrenomedullin levels by gene transfer to Panc-1 cells increased, whereas adrenomedullin small hairpin RNA silencing in MPanc96 cells inhibited tumor growth and metastasis in vivo.