The truncated somatostatin receptor sst5TMD4 stimulates the angiogenic process and is associated with lymphatic metastasis and poor prognosis in breast cancer patients

ABSTRACT: The presence of the truncated somatostatin receptor sst5TMD4 is associated with poor prognosis in breast cancers and increases malignancy in breast cancer cell lines. The objective of this study was to examine the cellular and molecular mechanisms underlying this association in order to identify new molecular targets for diagnosis, prognosis or therapy of these tumors. Therefore, a gene expression array was implemented using sst5TMD4 stably-transfected MCF-7 cells and their respective controls (empty plasmid); which revealed the existence of a profound alteration in the expression of genes involved in several tumoral processes such as cell survival or angiogenesis. Further characterization of sst5TMD4-overexpressing MCF-7 cells demonstrated increased expression/production of key pro-angiogenic factors and enhanced capacity to form mammospheres. These data were confirmed in a xenograft model of in vivo tumoral growth, where inoculation of sst5TMD4 transfected MCF-7 cells induced tumors with higher levels of VEGF and elevated number of blood vessels. Finally, sst5TMD4 was found to be expressed in a subset of human breast cancer samples where it correlated with angiogenic markers (VEGF, Angiopoietin-1 and CD34), the presence of lymphatic metastasis and disease-free survival of the breast cancer patients. Altogether, these data demonstrate a key role of the truncated sst5TMD4 receptor in the control of the angiogenic process during breast cancer progression. Therefore, these results support the role of sst5TMD4 in tumor malignancy and metastatic potential in breast cancers and may help to identifying new lines of actions for future drug therapies for these tumors. Four independent passages from stably-transfected sst5TMD4-pCDNA3.1 and empty-pCDNA3.1 vector, used as control (mock), MFC7 cells were used.

ORGANISM(S): Homo sapiens

SUBMITTER: Gema Moreno-Bueno 

PROVIDER: E-GEOD-85150 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress