Is acetylcholine a signaling molecule for human colon cancer progression?

Objective: Non-neuronal acetylcholine (ACh) has been suggested to be a mediator for the development of various types of cancer. We analyzed a possible role for this molecule in carcinogenesis and/or progression of human colon cancer, in patient biopsies harvested from the colon during surgery. We addressed whether ACh synthesis (by choline acetyltransferase) and/or degradation (by ACh esterase), as well as the expression of the α7-subtype of the nicotinic ACh receptors, and the peptide ligand at the α7 receptors, secreted mammalian Ly6/urokinase-type plasminogen activator receptor-related protein-1, respectively, are deranged in tumor tissue as compared with macroscopically tumor-free colon tissue.

A pharmacological analysis of the cholinergic regulation of urokinase-type plasminogen activator secretion in the human colon cancer cell line, HT-29.

Urokinase-type plasminogen activator (uPA) is an important factor for tumour cell invasion and metastasis. We recently showed that acetylcholine is an autocrine/paracrine growth factor for the human colon cancer cell line, HT-29, in part via the α7 subtype of the nicotinic acetylcholine receptors. In the current study, we investigated whether acetylcholine participates in the regulation of the protein expressions of also uPA and its receptor (uPAR) in the HT-29 cell line.

Nicotine induced modulation of SLURP-1 expression in human colon cancer cells.

The secreted mammalian Ly-6/urokinase plasminogen activator receptor-related protein-1 (SLURP-1) is an endogenous ligand at the alpha 7 subunit of the nicotinic acetylcholine receptor (nAChR). SLURP-1 has anti-tumourigenic properties. In the current study, we demonstrate that the challenge of HT-29 human colon cancer cells with nicotine for 24 h to increase cell growth via the alpha 7nAChRs, caused a marked reduction of the protein expression of SLURP-1.

Is acetylcholine an autocrine/paracrine growth factor via the nicotinic alpha7-receptor subtype in the human colon cancer cell line HT-29?

We used immunochemistry to demonstrate expression of acetylcholine's nicotinic alpha7-receptor subtype in human colon cancer cell line HT-29. Moreover, RT-PCR and immunochemistry showed that choline acetyltransferase and acetylcholine esterase, the enzymes responsible for acetylcholine synthesis and degradation, respectively, localise in HT-29 cells. Bromoacetylcholine bromide, an inhibitor of choline acetyltransferase, significantly attenuated basal cell growth.

Functional expression of mu-opioid receptors in the human colon cancer cell line, HT-29, and their localization in human colon.

We have investigated the functional expression of mu-opioid receptors (MORs) in the human colon cancer cell line, HT-29. As revealed by immunocytochemistry, immunoreactivity was present in both the cytoplasm and nuclei of the cells. Challenge with morphine for 24 h (1 nM to 1 microM) barely affected cell proliferation, while the secretion of urokinase type plasminogen activator (a protease involved in invasion/metastasis) was markedly augmented by a concentration of 0.

The effect of opioids on the development of postoperative intra-abdominal adhesions.

People addicted to opium rarely develop intra-abdominal adhesions after abdominal surgery. We aimed to evaluate the effect of opium or morphine on preventing postoperative adhesions in rats. Sixty-three rats were randomly divided into a control group, opium-addicted group, and morphine-addicted group in a double-blind study.

Effects of norepinephrine or prostaglandin E2 on extracellular acidification rate of MCG 101, or K1735-M2 tumor cells.

We studied by microphysiometry functional effects of two different signalling molecules in the murine tumor cell lines, MCG 101 and K1735-M2, namely norepinephrine (NE) and prostaglandin E2 (PGE2). This methodology implies estimation of intracellular metabolism by measurements of extracellular acidification rate (ECAR). MCG 101 (an undifferentiated, epithelial-like tumor), in contrast to K1735-M2 (a melanoma), has been found to produce great amounts of PGE2.

Expression of P2Y2 purinoceptors in MCG 101 murine sarcoma cells, and HT-29 human colon carcinoma cells.

We investigated how agonists at purinoceptors may affect tumour cell metabolism. This was investigated in vitro in tumour cell lines by microphysiometry, which method monitors extracellular acidification rate (ECAR), on-line. The cell lines investigated were the murine sarcoma, MCG 101, and the human colon cancer, HT-29.