IGPR-1 is a novel adhesion molecule involved in colorectal tumor growth
Woolf, Nicholas Taylor
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Colorectal cancer (CRC) is among the most prevalent and lethal cancers in the United States. The mechanisms by which tumor cells sense their microenvironment have profound importance in driving the progression of malignancy and evasion from treatment. Specialized microenvironment-sensing cell surface receptors such as cell adhesion molecules allow tumor cells to survey and respond to their microenvironment. We have recently identified a novel cell adhesion molecule named immunoglobulin-containing and proline-rich receptor 1 (IGPR-1) that is normally expressed in both endothelial and epithelial human cell types; however, its potential role in human malignancy remains unknown. To investigate the role IGPR-1 plays in CRC tumor growth, we overexpressed IGPR-1 in human HT29 and HCT116 colon adenocarcinoma cells and examined the effect of IGPR-1 on tumor growth and the mechanisms involved in a cell culture system. The data demonstrate that overexpression of IGPR-1 enhances CRC cell proliferation and survival in vitro. Furthermore, we demonstrate that the extracellular domain of IGPR-1 is required for its ability to support tumor growth. While deletion of the extracellular domain of IGPR-1 impaired its ability to promote tumor cell survival, stimulation of the chimeric IGPR-1 consisting of the extracellular domain of human colony stimulating factor-1 receptor (CSF-1R) fused to the transmembrane and cytoplasmic domains of IGPR-1 promoted tumor cell survival. Additionally, the presence of serine 186 and 220 in the cytoplasmic domain is important for IGPR-1 activity in tumor cells. This work identifies IGPR-1 as an important protein in the regulation of CRC cell growth and survival, and this makes it a possible therapeutic target in the clinical management of CRC.