Down-regulation of cannabinoid type 1 (CB1) receptor and its downstream signaling pathways in metastatic colorectal cancer

Valeria Tutino, Maria Gabriella Caruso, Valentina De Nunzio, Dionigi Lorusso, Nicola Veronese, Isabella Gigante, Maria Notarnicola, Gianluigi Giannelli

Research output: Contribution to journalArticle

Abstract

Changes in the regulation of endocannabinoid production, together with an altered expression of their receptors are hallmarks of cancer, including colorectal cancer (CRC). Although several studies have been conducted to understand the biological role of the CB1 receptor in cancer, little is known about its involvement in the metastatic process of CRC. The aim of this study was to investigate the possible link between CB1 receptor expression and the presence of metastasis in patients with CRC, investigating the main signaling pathways elicited downstream of CB1 receptor in colon cancer. Fifty-nine consecutive patients, with histologically proven colorectal cancer, were enrolled in the study, of which 30 patients with synchronous metastasis, at first diagnosis and 29 without metastasis. A low expression of CB1 receptor were detected in primary tumor tissue of CRC patients with metastasis and consequently, we observed an alteration of CB1 receptor downstream signaling. These signaling routes were also altered in intestinal normal mucosa, suggesting that, normal mucosa surrounding the tumor provides a realistic picture of the molecules involved in tissue malignant transformation. These observations contribute to the idea that drugs able to induce CB1 receptor expression can be helpful in order to set new anticancer therapeutic strategies.

Original languageEnglish
Article number708
JournalCancers
Volume11
Issue number5
DOIs
Publication statusPublished - May 2019

Fingerprint

Cannabinoid Receptors
Colorectal Neoplasms
Down-Regulation
Neoplasm Metastasis
Neoplasms
Endocannabinoids
Intestinal Mucosa
Colonic Neoplasms
Mucous Membrane
Pharmaceutical Preparations

Keywords

  • Cannabinoid type 1 (CB1) receptor
  • Colorectal cancer
  • Endocannabinoid system
  • Metastasis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

@article{fafe6204563e4c4ca81701a12c07f1ac,
title = "Down-regulation of cannabinoid type 1 (CB1) receptor and its downstream signaling pathways in metastatic colorectal cancer",
abstract = "Changes in the regulation of endocannabinoid production, together with an altered expression of their receptors are hallmarks of cancer, including colorectal cancer (CRC). Although several studies have been conducted to understand the biological role of the CB1 receptor in cancer, little is known about its involvement in the metastatic process of CRC. The aim of this study was to investigate the possible link between CB1 receptor expression and the presence of metastasis in patients with CRC, investigating the main signaling pathways elicited downstream of CB1 receptor in colon cancer. Fifty-nine consecutive patients, with histologically proven colorectal cancer, were enrolled in the study, of which 30 patients with synchronous metastasis, at first diagnosis and 29 without metastasis. A low expression of CB1 receptor were detected in primary tumor tissue of CRC patients with metastasis and consequently, we observed an alteration of CB1 receptor downstream signaling. These signaling routes were also altered in intestinal normal mucosa, suggesting that, normal mucosa surrounding the tumor provides a realistic picture of the molecules involved in tissue malignant transformation. These observations contribute to the idea that drugs able to induce CB1 receptor expression can be helpful in order to set new anticancer therapeutic strategies.",
keywords = "Cannabinoid type 1 (CB1) receptor, Colorectal cancer, Endocannabinoid system, Metastasis",
author = "Valeria Tutino and Caruso, {Maria Gabriella} and {De Nunzio}, Valentina and Dionigi Lorusso and Nicola Veronese and Isabella Gigante and Maria Notarnicola and Gianluigi Giannelli",
year = "2019",
month = "5",
doi = "10.3390/cancers11050708",
language = "English",
volume = "11",
journal = "Cancers",
issn = "2072-6694",
publisher = "MDPI AG",
number = "5",

}

TY - JOUR

T1 - Down-regulation of cannabinoid type 1 (CB1) receptor and its downstream signaling pathways in metastatic colorectal cancer

AU - Tutino, Valeria

AU - Caruso, Maria Gabriella

AU - De Nunzio, Valentina

AU - Lorusso, Dionigi

AU - Veronese, Nicola

AU - Gigante, Isabella

AU - Notarnicola, Maria

AU - Giannelli, Gianluigi

PY - 2019/5

Y1 - 2019/5

N2 - Changes in the regulation of endocannabinoid production, together with an altered expression of their receptors are hallmarks of cancer, including colorectal cancer (CRC). Although several studies have been conducted to understand the biological role of the CB1 receptor in cancer, little is known about its involvement in the metastatic process of CRC. The aim of this study was to investigate the possible link between CB1 receptor expression and the presence of metastasis in patients with CRC, investigating the main signaling pathways elicited downstream of CB1 receptor in colon cancer. Fifty-nine consecutive patients, with histologically proven colorectal cancer, were enrolled in the study, of which 30 patients with synchronous metastasis, at first diagnosis and 29 without metastasis. A low expression of CB1 receptor were detected in primary tumor tissue of CRC patients with metastasis and consequently, we observed an alteration of CB1 receptor downstream signaling. These signaling routes were also altered in intestinal normal mucosa, suggesting that, normal mucosa surrounding the tumor provides a realistic picture of the molecules involved in tissue malignant transformation. These observations contribute to the idea that drugs able to induce CB1 receptor expression can be helpful in order to set new anticancer therapeutic strategies.

AB - Changes in the regulation of endocannabinoid production, together with an altered expression of their receptors are hallmarks of cancer, including colorectal cancer (CRC). Although several studies have been conducted to understand the biological role of the CB1 receptor in cancer, little is known about its involvement in the metastatic process of CRC. The aim of this study was to investigate the possible link between CB1 receptor expression and the presence of metastasis in patients with CRC, investigating the main signaling pathways elicited downstream of CB1 receptor in colon cancer. Fifty-nine consecutive patients, with histologically proven colorectal cancer, were enrolled in the study, of which 30 patients with synchronous metastasis, at first diagnosis and 29 without metastasis. A low expression of CB1 receptor were detected in primary tumor tissue of CRC patients with metastasis and consequently, we observed an alteration of CB1 receptor downstream signaling. These signaling routes were also altered in intestinal normal mucosa, suggesting that, normal mucosa surrounding the tumor provides a realistic picture of the molecules involved in tissue malignant transformation. These observations contribute to the idea that drugs able to induce CB1 receptor expression can be helpful in order to set new anticancer therapeutic strategies.

KW - Cannabinoid type 1 (CB1) receptor

KW - Colorectal cancer

KW - Endocannabinoid system

KW - Metastasis

UR - http://www.scopus.com/inward/record.url?scp=85067209107&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067209107&partnerID=8YFLogxK

U2 - 10.3390/cancers11050708

DO - 10.3390/cancers11050708

M3 - Article

AN - SCOPUS:85067209107

VL - 11

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 5

M1 - 708

ER -