A soluble form of GAS1 inhibits tumor growth and angiogenesis in a triple negative breast cancer model.

Abstract

We previously demonstrated the capacity of GAS1 (Growth Arrest Specific 1) to inhibit the growth of gliomas by blocking the GDNF-RET signaling pathway. Here, we show that a soluble form of GAS1 (tGAS1), decreases the number of viable MDA MB 231 human breast cancer cells, acting in both autocrine and paracrine manners when secreted from producing cells. Moreover, tGAS1 inhibits the growth of tumors implanted in female nu/nu mice through a RET-independent mechanism which involves interfering with the Artemin (ARTN)-GFRα3-(GDNF Family Receptor alpha 3) mediated intracellular signaling and the activation of ERK. In addition, we observed that the presence of tGAS1 reduces the vascularization of implanted tumors, by preventing the migration of endothelial cells. The present results support a potential adjuvant role for tGAS1 in the treatment of breast cancer, by detaining tumor growth and inhibiting angiogenesis.

• Authors: Adriana Jiménez, Adolfo López-Ornelas, Enrique Estudillo, Lorenza González-Mariscal, Rosa O González, José Segovia
• Journal: Experimental cell research (Exp Cell Res) Vol. 327 Issue 2 Pg. 307-17 (Oct 01 2014) ISSN: 1090-2422 [Electronic] United States
• PMID: 24992044 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• ARTN protein, human
• Cell Cycle Proteins
• Culture Media, Conditioned
• GAS1 protein, human
• GPI-Linked Proteins
• Nerve Tissue Proteins
• RNA, Messenger

Topics

• Animals
• Apoptosis
• Blotting, Western
• Cell Cycle
• Cell Cycle Proteins (genetics, metabolism)
• Cell Movement
• Cell Proliferation
• Culture Media, Conditioned (pharmacology)
• Endothelium, Vascular (cytology, metabolism)
• Female
• Flow Cytometry
• Fluorescent Antibody Technique
• GPI-Linked Proteins (genetics, metabolism)
• Humans
• MAP Kinase Signaling System
• Mice
• Mice, Nude
• Neovascularization, Pathologic (prevention & control)
• Nerve Tissue Proteins (genetics, metabolism)
• Phosphorylation
• RNA, Messenger (genetics)
• Rats
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Triple Negative Breast Neoplasms (blood supply, metabolism, pathology, prevention & control)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays