Identifying The Physiological Actions Of Calcitonin
Funder
National Health and Medical Research Council
Funding Amount
$683,040.00
Summary
Calcitonin is a hormone whose main action has long been regarded as the slowing down of bone breakdown, however, its importance in human physiology is unknown. The aim of this study is to understand the role of calcitonin in regulating bone formation and protecting the skeleton in times of calcium stress, such as lactation. These results will greatly advance our understanding of the control of bone and calcium homeostasis, which will have implications for the treatment of bone disorders.
Breast cancer remains the major form of cancer diagnosed in women, and is still the leading cause of cancer death. There remains a pressing need to find better ways to treat this disease. Increasingly, cancer treatments will make use of a growing knowledge of the factors that normally regulate cell growth, and will apply this knowledge to make cancer cells more sensitive to existing anticancer treatments. We are proposing here to study the hormone calcitonin as a novel regulator of cancer cell g ....Breast cancer remains the major form of cancer diagnosed in women, and is still the leading cause of cancer death. There remains a pressing need to find better ways to treat this disease. Increasingly, cancer treatments will make use of a growing knowledge of the factors that normally regulate cell growth, and will apply this knowledge to make cancer cells more sensitive to existing anticancer treatments. We are proposing here to study the hormone calcitonin as a novel regulator of cancer cell growth. Calcitonin is better known as a hormone that inhibits bone loss, by acting on bone resorbing cells called osteoclasts. However, our present proposal is based on our recent finding that the receptor for calcitonin is for some reason also found in many breast cancers. Moreover, we have shown that calcitonin can potently inhibit the growth of cells that have the calcitonin receptor on their surface. We plan to extend these findings in 4 ways: 1 We will make use of a large bank of breast cancer samples at the Royal Adelaide Hospital to determine whether the presence of the calcitonin receptor in breast cancers is related to other features of the tumours, such as their propensity to spread to other organs. 2 We will investigate the mechanisms by which calcitonin slows the growth of cells. 3 We have unique access to new calcitonin-like molecules, called calcitonin mimetics, which we will investigate for the ability to inhibit cell growth. These molecules are much cheaper and probably easier to administer than calcitonin itself. 4 We will investigate whether treatment of cells with calcitonin makes them more sensitive to other anticancer treatments. We hope that success in this project will lead to a more detailed understanding of the way that molecules like calcitonin can regulate cell growth and to new treatment options for cancer.Read moreRead less
Receptors form a basic intermediary as the acceptor site for signals that are transmitted between the cells that make up our body. Modulation of receptors, therefore, forms a key target in our ability to treat disease. The largest class of receptors is the superfamily of G protein-coupled receptors (GPCRs), which transmit signals within a cell via proteins called G proteins. GPCRs form between 1 and 5% of the entire repertoire of human genes. One group of GPCRs provide the target for small prote ....Receptors form a basic intermediary as the acceptor site for signals that are transmitted between the cells that make up our body. Modulation of receptors, therefore, forms a key target in our ability to treat disease. The largest class of receptors is the superfamily of G protein-coupled receptors (GPCRs), which transmit signals within a cell via proteins called G proteins. GPCRs form between 1 and 5% of the entire repertoire of human genes. One group of GPCRs provide the target for small protein molecules that circulate through the body. One such circulating molecule is calcitonin, a peptide that plays an important role in maintaining circulating calcium levels in the body, which is essential for proper maintenance of the skeleton. As a consequence of this action, calcitonin is an important clinically used tool in the treatment of bone disease such as osteoporosis and Paget's disease. Due to the molecular nature of calcitonin and its receptor (and other related receptors) that have a broad, complex mechanism of interaction, we have very little definitive information on how calcitonin interfaces with its receptor to signal to target cells. The current project utilises a novel method of permanently linking calcitonin to its receptor, allowing identification of how the two components come together. This information provides important fundamentals for understanding how this and related receptors work and the potential for rational design of improved therapeutic tools.Read moreRead less