Bedside to Bench: Role of Muscarinic Receptor Activation in Ultrarapid Growth of Colorectal Cancer in a Patient With Pheochromocytoma

Abstract

An elderly man with long-standing, non-resectable pheochromocytoma rapidly developed rectal adenocarcinoma despite close endoscopic surveillance. We determined that the patient’s colorectal cancer over-expressed M3 subtype muscarinic receptors, whereas his pheochromocytoma expressed choline acetyltransferase, an enzyme required to produce acetylcholine, a muscarinic receptor agonist. These findings suggested that acetylcholine release from the pheochromocytoma stimulated rapid growth of the rectal neoplasm. As proof-of-principle, we demonstrate here that culture media conditioned by pheochromocytoma cells stimulates proliferation of a human colon cancer cell line, an effect attenuated by atropine, a muscarinic receptor inhibitor. Our observations provide both clinical and laboratory evidence that muscarinic receptor agonists promote the growth of colorectal neoplasia.

A patient suffered from not only MSI‐H colon cancer but also adrenal pheochromocytoma

“…Von Rosenvinge EC et al. reported an elderly man with long‐standing, nonresectable pheochromocytoma had rapid development of rectal adenocarcinoma despite close endoscopic surveillance [5]. But what's interesting about our patient is that the colon neoplasm was positive for MSH2, MSH6 and negative for MLH1, PMS2, and adrenal neoplasm was positive for MSH2, MSH6 and negative for MLH1, PMS2 by immunohistochemical analysis.…”

Optimal Management of a Synchronous Diagnosis of Phaeochromocytoma and Colorectal Neoplasia

“…It has been shown that adrenaline upregulates factors that increase the proliferation of colon cancer cells, while noradrenaline increases their locomotive capabilities [16,17]. In a patient with untreated, recurrent phaeochromocytoma [18], rectal adenocarcinoma occurred 12 years later. Immunohistochemical staining showed strong staining for choline acetyltransferase (ChAT), the principal enzyme for acetylcholine production.…”

Role of Muscarinic Acetylcholine Receptors in Breast Cancer: Design of Metronomic Chemotherapy

“…It has been reported that M 3 receptor is widely expressed in digestive tract cancer, and may play an important role in the proliferation, differentiation, transformation and carcinogenesis of tumors [39,42]. mAChR agonists promote the growth of colorectal neoplasia and findings suggest that vagal innervation contributes to gastric tumorigenesis via M 3 receptor mediated Wnt signaling [41,43].…”