Expression And Functional Studies On The Novel Ovarian-expressed Serine Protease, Kallikrein 4, In Ovarian Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$410,250.00
Summary
Ovarian cancer is the leading cause of death from gynaecologic malignancies. In Australia, it is the most life-threatening of all gynaecological cancers. The major reason why the death rate has improved little in the last two decades is that ovarian cancer is detected too late and the type of treatment is not very effective. In this research, we are looking at a new protein, called the K4 protein, which belongs to the same family as the PSA enzyme that is used in the PSA test for prostate cancer ....Ovarian cancer is the leading cause of death from gynaecologic malignancies. In Australia, it is the most life-threatening of all gynaecological cancers. The major reason why the death rate has improved little in the last two decades is that ovarian cancer is detected too late and the type of treatment is not very effective. In this research, we are looking at a new protein, called the K4 protein, which belongs to the same family as the PSA enzyme that is used in the PSA test for prostate cancer. Our preliminary findings suggest that K4 is increased in the serous type ovarian cancer tumours so we intend to determine if K4 will be a useful bio-marker for this type of ovarian cancer. We also have made some interesting findings of some novel forms of the K4 protein and gene in ovarian cancer tissues and we intend to characterise these further to see if they might also be useful in detection of this disease. We are also studying the function and localisation of these different forms of K4 in cancer cells, to identify the exact role the enzyme performs in cancer development. These latter studies will help us understand the disease process better and may help us design new treatment approaches.Read moreRead less
Cell polarity is the property of cells to be spatially oriented in a tissue or organ. We have now shown that the gene Scribble, a key regulator of cell orientation, may keep tumour development in check. In this proposal, we will examine how disruption of Scribble promotes cancer using a combination of tissue culture studies and a newly established mouse model. Understanding how this new pathway can regulate tumour development may provide novel targets for therapeutic intervention in cancer.
Much of the death and suffering caused by cancer is associated with secondary tumours, but alot remains to be learned about how cancer spreads through the patient's body. This project will determine how genes that enable the growth of tumours work with other genes that enable cancer cells to detach from the tumour, enabling them to enter the bloodstream and form secondary tumours in other organs.
Interstitially Invasive Trophoblast Of The Murine Placenta: Developmental Origins, Functions And Gene Expression.
Funder
National Health and Medical Research Council
Funding Amount
$369,717.00
Summary
Due to the obvious limitations to studying human pregnancy, the mouse has become a valuable model. However, invasion of the placenta into the uterine wall and vasculature, critical for successful pregnancy, is poorly understood in the mouse. The aims of the proposal are designed to gain a better understanding of these processes in mice and will provide a more accurate model system to study serious pregnancy complications resulting from abnormal placental invasion, such as preeclampsia.
Reevaluation Of The Anatomy Of The Human Lymphatic Vessel Network
Funder
National Health and Medical Research Council
Funding Amount
$539,750.00
Summary
The mode of spread of cancer cells from a primary tumour to other parts of the body is still not completely understood, although the lymphatic system is known to be important in this process. Lymph vessels are tiny transparent channels that form a network over the entire body. They transport tissue fluid to regional lymph glands in the neck, armpits, groin, chest and abdomen where the immune response maybe initiated to combat foreign agents such as bacteria and cancer cells. Current knowledge of ....The mode of spread of cancer cells from a primary tumour to other parts of the body is still not completely understood, although the lymphatic system is known to be important in this process. Lymph vessels are tiny transparent channels that form a network over the entire body. They transport tissue fluid to regional lymph glands in the neck, armpits, groin, chest and abdomen where the immune response maybe initiated to combat foreign agents such as bacteria and cancer cells. Current knowledge of the anatomy of these tiny vessels is based on work done by Sappey more than a century ago. There is an urgent need to update this work as many of his conclusions have been found to be inaccurate. We will use our pioneering methods of microsurgical tissue transfer- now being used worldwide - and our extensive experience in delineating fine channels, to address some of the basic questions about the anatomical pathways of spread of cancer. We hope to discover for example: why cancer on one side of the back can spread to glands in the opposite groin or armpit, thought by Sappey to be impossible; why cancer on one side of the tongue can spread to lymph glands on the opposite side of the neck; and why there is sometimes swelling of the limbs following lymph gland ablation by surgery or radiotherapy of glands in the groin or armpit. Currently it is thought that the only major connections with the venous system are at the base of the neck. Our initial work has shown unexpected connections with blood vessels in the periphery and unreported lymphatic vessel pathways between the skin and deep tissues. The results of this research will give information that will aid in localizing and treating the spread of malignancies and will underlie future treatment of obstructed lymph vessels that are the cause of painful, disabling swelling (lymphoedema) of the limbs.Read moreRead less
CSF-1 Regulation Of Macrophage Adhesion And Motility And Promotion Of Tumour Invasion And Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$323,453.00
Summary
Macrophages, a type of white blood cell, infiltrate tumours and encourage tumour cells to metastasize. The mechanism involves secretion of a macrophage motility factor, CSF-1, by the tumour cells and secretion of a tumour cell motility factor by the macrophages to stimulate co-migration, invasion and metastasis. CSF-1 controls macrophage motility via the CSF-1 receptor. Dissection of receptor signalling pathways to macrophage motility will identify therapeutic targets to prevent tumour spread.
Role Of A Novel Tks5-Nck Signaling Pathway In Cancer Invasion
Funder
National Health and Medical Research Council
Funding Amount
$560,434.00
Summary
Invasion and metastasis are major causes of death in cancer patients. Our research has uncovered a pathway that increases the invasive potential of tumour cells in vitro. We now aim to determine if the pathway is relevant in invasion and metastasis in clinically relevant models; how a drug targeting the pathway affects invasion and; the extent to which the pathway is active in human tumours. These studies may identify a new molecular target for anti-invasive drugs.
Elucidation Of Signalling Enzymes Regulating The Small GTPase RhoA
Funder
National Health and Medical Research Council
Funding Amount
$226,320.00
Summary
Many normal and pathological processes in the human body depend on the ability of cells to attach to a biological surface (adhesion), spread out, or move to another site (migration). Examples of biological processes that require such events include the division and arrangement of cells in a developing embryo, or the ability of cancer cells to spread (metastasise). A driving force behind the attachment or movement of cells is their ability to rearrange a scaffolding called the cytoskeleton. The c ....Many normal and pathological processes in the human body depend on the ability of cells to attach to a biological surface (adhesion), spread out, or move to another site (migration). Examples of biological processes that require such events include the division and arrangement of cells in a developing embryo, or the ability of cancer cells to spread (metastasise). A driving force behind the attachment or movement of cells is their ability to rearrange a scaffolding called the cytoskeleton. The cytoskeleton is similar to the skeleton of the human body, in that it acts to maintain cell shape and rigidity. However, it is also actively reorganised to participate in many cellular processes, including cell attachment and movement. By furthering our understanding of how the cytoskeleton is rearranged, this will provide important insights not only into the basics of cell behaviour, but will also have important implications for a number of human disease states. This proposal aims to investigate mechanisms that regulate the reorganisation of the cytoskeleton. It is well established that the rearrangement of this scaffolding, in many different types of cells, is controlled by a family of proteins called the Rho family of small GTPases. One of the members of this family, RhoA, has a specific role in controlling cell attachment, and interestingly, has been implicated in the invasive and metastatic properties of human tumour cells. We have recently identified a protein that is responsible for controlling the activation of RhoA. This proposal aims to further our understanding of how this protein regulates RhoA, and therefore cell attachment and movement. Given that cell attachment and movement are important events contributing to the spread of tumours, this study may provide important insight into alternative approaches of controlling cell movement, and ultimately malignant progression.Read moreRead less
New Role For The E3 Ligase E6AP In The Control Of Cell Motility And Invasion
Funder
National Health and Medical Research Council
Funding Amount
$462,162.00
Summary
Cell motility and invasion are fundamental process in normal cellular functions, however, when deregulated they can lead to metastatic cancer, a leading cause of cancer mortality and morbidity worldwide. Detailed understanding of the mechanisms governing these processes is essential for the development of new targets to prevent metastatic cancer. We discovered a protein that control these processes, which renders it an important target to investigate.