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Open AccessArticle

Down-Regulation of Cannabinoid Type 1 (CB1) Receptor and its Downstream Signaling Pathways in Metastatic Colorectal Cancer

1
Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology “S. de Bellis”, Research Hospital, Castellana Grotte, 70013 Bari, Italy
2
Ambulatory of Clinical Nutrition, National Institute of Gastroenterology “S. de Bellis”, Research Hospital, Castellana Grotte, 70013 Bari, Italy
3
Surgery Unit, National Institute of Gastroenterology “S. de Bellis”, Research Hospital, Castellana Grotte, 70013 Bari, Italy
4
Scientific Direction, National Institute of Gastroenterology “S. de Bellis”, Research Hospital, Castellana Grotte, 70013 Bari, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2019, 11(5), 708; https://doi.org/10.3390/cancers11050708
Received: 25 March 2019 / Revised: 15 May 2019 / Accepted: 20 May 2019 / Published: 22 May 2019
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. View Full-Text
Keywords: endocannabinoid system; cannabinoid type 1 (CB1) receptor; colorectal cancer; metastasis endocannabinoid system; cannabinoid type 1 (CB1) receptor; colorectal cancer; metastasis
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Tutino, V.; Caruso, M.G.; De Nunzio, V.; Lorusso, D.; Veronese, N.; Gigante, I.; Notarnicola, M.; Giannelli, G. Down-Regulation of Cannabinoid Type 1 (CB1) Receptor and its Downstream Signaling Pathways in Metastatic Colorectal Cancer. Cancers 2019, 11, 708.

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