Acetylcholine Receptor Expression in Merkel Cell Carcinoma

Bowers, Jeremy W.; Schlauder, Scott; Calder, Kenneth B.; Morgan, Michael B.

doi:10.1097/dad.0b013e31816797e4

Cited by 10 publications

(4 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As shown in Table 1, muscarinic receptor expression is reported in tissues and cell lines derived from cancer of the brain (58) lung (114,115), ovary (93), pancreas (2,116), prostate (8,84), skin (15,16,108), stomach (76), and uterus (116). Nonetheless, because muscarinic receptor expression is common if not ubiquitous in all tissues, simply demonstrating expression of muscarinic receptors is insufficient to conclude that muscarinic signaling plays an important role in cancer progression.…”

Section: Proposed Criteria To Validate Muscarinic Receptor-mediated Amentioning

confidence: 92%

Muscarinic receptors and ligands in cancer

Shah¹,

Khurana²,

Cheng³

et al. 2009

American Journal of Physiology-Cell Physiology

132

114

View full text Add to dashboard Cite

Emerging evidence indicates that muscarinic receptors and ligands play key roles in regulating cellular proliferation and cancer progression. Both neuronal and nonneuronal acetylcholine production results in neurocrine, paracrine, and autocrine promotion of cell proliferation, apoptosis, migration, and other features critical for cancer cell survival and spread. The present review comprises a focused critical analysis of evidence supporting the role of muscarinic receptors and ligands in cancer. Criteria are proposed to validate the biological importance of muscarinic receptor expression, activation, and postreceptor signaling. Likewise, criteria are proposed to validate the role of nonneuronal acetylcholine production in cancer. Dissecting cellular mechanisms necessary for muscarinic receptor activation as well as those needed for acetylcholine production and release will identify multiple novel targets for cancer therapy.

show abstract

Section: Proposed Criteria To Validate Muscarinic Receptor-mediated Amentioning

confidence: 92%

Muscarinic receptors and ligands in cancer

Shah¹,

Khurana²,

Cheng³

et al. 2009

American Journal of Physiology-Cell Physiology

132

114

View full text Add to dashboard Cite

show abstract

“…By immunohistochemistry, Bowers et al (2008) reported that 15 of 15 primary cutaneous cases of Merkel cell carcinoma expressed M3 and M5 receptors. Given that the proliferation of other types of neuroendocrine cells such as pulmonary neuroendocrine cells that express muscarinic receptors can be inhibited by M3 antagonists, this would suggest that muscarinic antagonists might also inhibit growth of Merkel Cell Carcinomas, but this again needs to be determined.…”

Section: Muscarinic Receptors and Specific Cancersmentioning

confidence: 99%

Muscarinic Receptor Agonists and Antagonists: Effects on Cancer

Spindel

2011

Handbook of Experimental Pharmacology

View full text Add to dashboard Cite

Many epithelial and endothelial cells express a cholinergic autocrine loop in which acetylcholine acts as a growth factor to stimulate cell growth. Cancers derived from these tissues similarly express a cholinergic autocrine loop and ACh secreted by the cancer or neighboring cells interacts with M3 muscarinic receptors expressed on the cancer cells to stimulate tumor growth. Primary proliferative pathways involve MAPK and Akt activation. The ability of muscarinic agonists to stimulate, and M3 antagonists to inhibit tumor growth has clearly been demonstrated for lung and colon cancer. The ability of muscarinic agonists to stimulate growth has been shown for melanoma, pancreatic, breast, ovarian, prostate and brain cancers, suggesting that M3 antagonists will also inhibit growth of these tumors as well. As yet no clinical trials have proven the efficacy of M3 antagonists as cancer therapeutics, though the widespread clinical use and low toxicity of M3 antagonists support the potential role of these drugs as adjuvants to current cancer therapies.

show abstract

“…Although the roles of MRs in conferring malignancy to various tumour cells is a widely pursued hypothesis [6,7,8,26], in case of the skin the interpretation became somewhat difficult, as in the meantime the presence of all five MRs was described in healthy melanocytes and their functionality was also proven [4]. Recently the role of the nonneural cholinergic signalization in the physiological and pathological skin functions became widely accepted (see [5] and for recent reviews [27,28]).…”

Section: Muscarinic Acetylcholine Receptors Is Melanoma Cellsmentioning

confidence: 99%

Cytoplasmic Ca2+ concentration changes evoked by muscarinic cholinergic stimulation in primary and metastatic melanoma cell lines

et al. 2011

View full text Add to dashboard Cite

Experiments were performed to explore differences between cultured primary and metastatic melanoma cell lines in their muscarinic acetylcholine receptor-mediated intracellular Ca signalization. The expression of type 1 and type 3 muscarinic receptors was detected and compared at the protein level using both immunocytochemistry and semiquantitative western blotting. The functionality of muscarinic receptors was tested by applying carbamylcholine (CCh; 1 mmol/l) and by recording the associated increases in cytoplasmic Ca using Ca imaging with the application of the Ca indicator dye, fluo-4. These data indicate that the expression levels of the receptor proteins were not significantly different in the metastatic (HT199, HT168-M1) and the primary (WM35) cell lines. Although Ca transients were evoked in all the three cell lines by CCh, the proportion of the CCh-positive cells was smaller amongst the WM35 cells. The Ca transients could be effectively blocked by atropine (0.1 mmol/l). The time courses of the Ca transients were highly variable, and in some instances they showed a late (plateau-like) component whose presence crucially depended on the influx of extracellular Ca. When the extracellular Ca concentration was reduced, the duration of the CCh-evoked transients was considerably decreased; a phenomenon that was more pronounced in the metastatic cell lines. Although there are no fundamental differences in the muscarinic receptor-mediated Ca signalization of the primary and metastatic cell lines, the quantitative differences showed in this study may partially explain the increased malignancy and migratory potential of the metastatic cells.

show abstract

Acetylcholine Receptor Expression in Merkel Cell Carcinoma

Cited by 10 publications

References 10 publications

Muscarinic receptors and ligands in cancer

Muscarinic receptors and ligands in cancer

Muscarinic Receptor Agonists and Antagonists: Effects on Cancer

Cytoplasmic Ca2+ concentration changes evoked by muscarinic cholinergic stimulation in primary and metastatic melanoma cell lines

Contact Info

Product

Resources

About