title: The truncated somatostatin receptor sst5TMD4 stimulates the angiogenic process and is associated to lymphatic metastasis and disease-free survival in breast cancer patients.
abstract: The truncated somatostatin receptor sst5TMD4 is associated with poor prognosis in breast cancer and increases breast cancer cell malignancy. Here, we examined the cellular/molecular mechanisms underlying this association, aiming to identify new molecular tools to improve diagnosis, prognosis or therapy. A gene expression array comparing sst5TMD4 stably-transfected MCF-7 cells and their controls (empty-plasmid) revealed the existence of profound alterations in the expression of genes involved in key tumoral processes, such as cell survival or angiogenesis. Moreover, sst5TMD4-overexpressing MCF-7 and MDA-MB-231 cells demonstrated increased expression/production of pro-angiogenic factors and enhanced capacity to form mammospheres. Consistently, sst5TMD4-expressing MCF-7 cells induced xenografted tumors with higher VEGF levels and elevated number of blood vessels. Importantly, sst5TMD4 was expressed in a subset of breast cancers, where it correlated with angiogenic markers, lymphatic metastasis, and reduced disease-free survival. These results, coupled to our previous data, support a relevant role of sst5TMD4 in the angiogenic process and reinforce the role of sst5TMD4 in breast cancer malignancy and metastatic potential, supporting its possible utility to develop new molecular biomarkers and drug therapies for these tumors.
authors: Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain.|Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain.|Reina Sofia University Hospital (HURS), Cordoba, Spain.|CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Cordoba, Spain.
authors: Manuel D
authors: MD
authors: Gahete
authors: Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain.|Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain.|Reina Sofia University Hospital (HURS), Cordoba, Spain.|CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Cordoba, Spain.
authors: David
authors: D
authors: Rincón-Fernández
authors: Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain.
authors: Mario
authors: M
authors: Durán-Prado
authors: Department of Biochemistry, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas "Alberto Sols" (CSIC-UAM), IdiPAZ, MD Anderson Internacional Foundation, Madrid, Spain.
authors: Marta
authors: M
authors: Hergueta-Redondo
authors: Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain.|Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain.|Reina Sofia University Hospital (HURS), Cordoba, Spain.|CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Cordoba, Spain.
authors: Alejandro
authors: A
authors: Ibáñez-Costa
authors: Pathology Deparment, MD Anderson Cancer Center, Madrid, Spain.
authors: Alejandro
authors: A
authors: Rojo-Sebastián
authors: Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain.|Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain.|Reina Sofia University Hospital (HURS), Cordoba, Spain.|CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Cordoba, Spain.
authors: Francisco
authors: F
authors: Gracia-Navarro
authors: IPSEN Bioscience, Cambridge, Massachusetts, USA.
authors: Michael D
authors: MD
authors: Culler
authors: Tumor Angiogenesis Group, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
authors: Oriol
authors: O
authors: Casanovas
authors: Department of Biochemistry, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas "Alberto Sols" (CSIC-UAM), IdiPAZ, MD Anderson Internacional Foundation, Madrid, Spain.
authors: Gema
authors: G
authors: Moreno-Bueno
authors: Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain.|Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain.|Reina Sofia University Hospital (HURS), Cordoba, Spain.|CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Cordoba, Spain.
authors: Raúl M
authors: RM
authors: Luque
authors: Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain.|Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain.|Reina Sofia University Hospital (HURS), Cordoba, Spain.|CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Cordoba, Spain.
authors: Justo P
authors: JP
authors: Castaño
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D061986:MCF-7 Cells; D008819:Mice, Nude; D008875:Middle Aged; D009154:Mutation; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics* / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D014408:Biomarkers, Tumor; D017481:Receptors, Somatostatin; C094573:somatostatin receptor 5
keywords: VEGF; angiogenesis; breast cancer; somatostatin receptor; sst5TMD4