A possible new target in lung-cancer cells: The orphan receptor, bombesin receptor subtype-3

Peptides. 2018 Mar;101:213-226. doi: 10.1016/j.peptides.2018.01.016. Epub 2018 Feb 2.

Abstract

Human bombesin receptors, GRPR and NMBR, are two of the most frequently overexpressed G-protein-coupled-receptors by lung-cancers. Recently, GRPR/NMBR are receiving considerable attention because they act as growth factor receptors often in an autocrine manner in different lung-cancers, affect tumor angiogenesis, their inhibition increases the cytotoxic potency of tyrosine-kinase inhibitors reducing lung-cancer cellular resistance/survival and their overexpression can be used for sensitive tumor localization as well as to target cytotoxic agents to the cancer. The orphan BRS-3-receptor, because of homology is classified as a bombesin receptor but has received little attention, despite the fact that it is also reported in a number of studies in lung-cancer cells and has growth effects in these cells. To address its potential importance, in this study, we examined the frequency/relative quantitative expression of human BRS-3 compared to GRPR/NMBR and the effects of its activation on cell-signaling/growth in 13 different human lung-cancer cell-lines. Our results showed that BRS-3 receptor is expressed in 92% of the cell-lines and that it is functional in these cells, because its activation stimulates phospholipase-C with breakdown of phosphoinositides and changes in cytosolic calcium, stimulates ERK/MAPK and stimulates cell growth by EGFR transactivation in some, but not all, the lung-cancer cell-lines. These results suggest that human BRS-3, similar to GRPR/NMBR, is frequently ectopically-expressed by lung-cancer cells in which, it is functional, affecting cell signaling/growth. These results suggest that similar to GRPR/NMBR, BRS-3 should receive increased attention as possible approach for the development of novel treatments and/or diagnosis in lung-cancer.

Keywords: BRS-3; Bombesin; Bombesin related peptides; Gastrin-releasing peptide; Lung-cancer cells; Neuromedin B.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • BALB 3T3 Cells
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • MAP Kinase Signaling System*
  • Mice
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Receptors, Bombesin / biosynthesis*
  • Receptors, Bombesin / genetics
  • Transcriptional Activation*

Substances

  • Neoplasm Proteins
  • Receptors, Bombesin
  • bombesin receptor subtype 3