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

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Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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