GPCRomics: GPCR Expression in Cancer Cells and Tumors Identifies New, Potential Biomarkers and Therapeutic Targets

Paul A. Insel; Krishna Sriram; Shu Z. Wiley; Andrea Wilderman; Trishna Katakia; Thalia McCann; Hiroshi Yokouchi; Lingzhi Zhang; Ross Corriden; Dongling Liu; Michael Feigin; Randall P. French; Andrew M. Lowy; Fiona Murray

doi:10.3389/fphar.2018.00431

GPCRomics: GPCR Expression in Cancer Cells and Tumors Identifies New, Potential Biomarkers and Therapeutic Targets

Paul A. Insel^* (Corresponding Author), Krishna Sriram, Shu Z. Wiley, Andrea Wilderman, Trishna Katakia, Thalia McCann, Hiroshi Yokouchi, Lingzhi Zhang, Ross Corriden, Dongling Liu, Michael Feigin, Randall P. French, Andrew M. Lowy, Fiona Murray

^*Corresponding author for this work

Medical Sciences

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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 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 cancer 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.

Original language	English
Article number	431
Number of pages	11
Journal	Frontiers in Pharmacology
Volume	9
Early online date	22 May 2018
DOIs	https://doi.org/10.3389/fphar.2018.00431
Publication status	Published - 22 May 2018

Bibliographical note

Financial support for these studies was provided by Roche, the Lymphoma and Leukemia Society, Friends of ANCHOR, an ASPET Astellas Award and grants from the National Institutes of Health, National Cancer Institute (CA189477, CA121938, CA155620). National Cancer Institute (NCI) Therapeutic Training Grant 5T32CA121938, NIH/NCI Research Grants R21 CA189477, an ASPET David
Lehr Award and the Padres Pedal the Cause #PTC2017 award.

Keywords

breast cancer
Cancer microenvironment
chronic lymphocytic leukemia
Colon Cancer
GPCR array
Orphan receptors
Pancreatic Cancer

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10.3389/fphar.2018.00431Licence: CC BY

GPCRomics: GPCR Expression in Cancer Cells and Tumors Identifies New, Potential Biomarkers and Therapeutic Targets
© 2018 Insel, Sriram, Wiley, Wilderman, Katakia, McCann, Yokouchi, Zhang, Corriden, Liu, Feigin, French, Lowy and Murray. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. https://creativecommons.org/licenses/by/4.0/
Final published version, 1.61 MBLicence: CC BY

Fiona Murray
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Insel, P. A., Sriram, K., Wiley, S. Z., Wilderman, A., Katakia, T., McCann, T., Yokouchi, H., Zhang, L., Corriden, R., Liu, D., Feigin, M., French, R. P., Lowy, A. M., & Murray, F. (2018). GPCRomics: GPCR Expression in Cancer Cells and Tumors Identifies New, Potential Biomarkers and Therapeutic Targets. Frontiers in Pharmacology, 9, Article 431. https://doi.org/10.3389/fphar.2018.00431

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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 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 cancer 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.",

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note = "Financial support for these studies was provided by Roche, the Lymphoma and Leukemia Society, Friends of ANCHOR, an ASPET Astellas Award and grants from the National Institutes of Health, National Cancer Institute (CA189477, CA121938, CA155620). National Cancer Institute (NCI) Therapeutic Training Grant 5T32CA121938, NIH/NCI Research Grants R21 CA189477, an ASPET David Lehr Award and the Padres Pedal the Cause #PTC2017 award.",

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AU - Insel, Paul A.

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AU - Wilderman, Andrea

AU - Katakia, Trishna

AU - McCann, Thalia

AU - Yokouchi, Hiroshi

AU - Zhang, Lingzhi

AU - Corriden, Ross

AU - Liu, Dongling

AU - Feigin, Michael

AU - French, Randall P.

AU - Lowy, Andrew M.

AU - Murray, Fiona

N1 - Financial support for these studies was provided by Roche, the Lymphoma and Leukemia Society, Friends of ANCHOR, an ASPET Astellas Award and grants from the National Institutes of Health, National Cancer Institute (CA189477, CA121938, CA155620). National Cancer Institute (NCI) Therapeutic Training Grant 5T32CA121938, NIH/NCI Research Grants R21 CA189477, an ASPET David Lehr Award and the Padres Pedal the Cause #PTC2017 award.

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N2 - 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 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 cancer 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.

AB - 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 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 cancer 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.

KW - breast cancer

KW - Cancer microenvironment

KW - chronic lymphocytic leukemia

KW - Colon Cancer

KW - GPCR array

KW - Orphan receptors

KW - Pancreatic Cancer

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DO - 10.3389/fphar.2018.00431

M3 - Article

SN - 1663-9812

VL - 9

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

M1 - 431

ER -

GPCRomics: GPCR Expression in Cancer Cells and Tumors Identifies New, Potential Biomarkers and Therapeutic Targets

Abstract

Bibliographical note

Keywords

UN SDGs

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Fiona Murray

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