Abstract
G protein-coupled receptors (GPCRs), the largest family of targets for approved drugs, are rarely targeted for cancer treatment, except for certain endocrine and hormone-responsive tumors. Limited knowledge regarding GPCR expression in cancer cells likely has contributed to this lack of use of GPCR-targeted drugs as cancer therapeutics. We thus undertook GPCRomic studies to define the expression of endoGPCRs (which respond to endogenous molecules such as hormones, neurotransmitters and metabolites) in multiple types of cancer cells. Using TaqMan qPCR arrays to quantify the mRNA expression of ∼340 such GPCRs, we found that human chronic lymphocytic leukemia (CLL) cells/stromal cells associated with CLL, breast cancer cell lines, colon cancer cell lines, pancreatic ductal adenocarcinoma (PDAC) cells, cancer associated fibroblasts (CAFs), and PDAC tumors express 50 to >100 GPCRs, including many orphan GPCRs (which lack known physiologic agonists). Limited prior data exist regarding the expression or function of most of the highly expressed GPCRs in these cancer cells and tumors. Independent results from public cancer gene expression databases confirm the expression of such GPCRs. We propose that highly expressed GPCRs in cancer cells (for example, GPRC5A in PDAC and colon cancer cells and GPR68 in PDAC CAFs) may contribute to the malignant phenotype, serve as biomarkers and/or may be novel therapeutic targets for the treatment of cancer.
Highlights
Knowledge regarding the biology of tumors and malignant cells has greatly expanded in recent years
The results here show that data from Taqman G protein-coupled receptor (GPCR) arrays and High throughput RNA sequencing (RNA-seq) identify similar numbers of GPCRs in breast and colon cancers cells and in Pancreatic Ductal Adenocarcinoma (PDAC) tumors and pancreatic Cancer-Associated Fibroblasts (CAFs)
A key conclusion from our studies is that each type of cancer cell/tumor expresses a common set of GPCRs
Summary
Knowledge regarding the biology of tumors and malignant cells has greatly expanded in recent years. Increased understanding of the immune suppression that contributes to tumor growth and metastasis and development of therapeutics directed at this immune suppression have yielded improved clinical outcomes for a variety of cancers (Cogdill et al, 2017; Gotwals et al, 2017; Lim and June, 2017). In spite of such progress, new therapies are needed for most cancers. As plasma membrane proteins, GPCRs should be targetable as are numerous other types of cell surface proteins in various cancers
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