Proteolytic And Non-proteolytic Roles For PSA And Related Kallikrein Serine Proteases In Prostate Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$480,128.00
Summary
Prostate cancer is the most frequently occurring cancer in men in Western countries. Prostate cancer metastasis to bone and other organs is the painful end stage of this disease. The level of prostate specific antigen (PSA) in blood is often used as a marker of prostate cancer. PSA is one of 15 related enzymes in the kallikrein family of enzymes, which may be involved in breakdown of the tissue that surrounds cells in the prostate. As prostate cancer metastasis first requires spread from the pri ....Prostate cancer is the most frequently occurring cancer in men in Western countries. Prostate cancer metastasis to bone and other organs is the painful end stage of this disease. The level of prostate specific antigen (PSA) in blood is often used as a marker of prostate cancer. PSA is one of 15 related enzymes in the kallikrein family of enzymes, which may be involved in breakdown of the tissue that surrounds cells in the prostate. As prostate cancer metastasis first requires spread from the primary tumour and out of the prostate, it is possible that high production of these kallikrein enzymes by prosttae cancer cells may increase the ability of these cells to metastasise. In previous work, we have studied prostate cancer cells that we have engineered to make the kallikreins, PSA and kallikrein 4. Those cells that make PSA or kallikrein 4 are more elongated in shape and are better able to move across a porous barrier. Another important change is that these cells stop producing a protein that is usually found on the surface of these cells and is important for helping cells to stay attached to each other. When this protein is lost, these tumour cells no longer stay attached to each other and are more likely to move out of the prostate and spread into other parts of the body. The changes we observed in the cells that produce PSA and kallikrein 4 are typical of these more aggressive cancer cells. In this project, we will look at how PSA and kallikrein 4 cause the cells to undergo these changes. The majority of prostate cancer deaths arise from cancer that has spread from the primary tumour and out of the prostate capsule. This project aims to further understand the causes of prostate cancer spread and metastasis. This is a vital research priority if we are to address the mortality associated with prostate cancer metastasis and may lead to new treatment approaches for advanced metastic prostate cancer.Read moreRead less
Characterisation Of A Novel Prostate-expressed Kallikrein-like Protease And Its Target Proteins
Funder
National Health and Medical Research Council
Funding Amount
$724,544.00
Summary
Prostate disease is common in most men in later life and can affect their quality of life adversely. The primary conditions are benign prostatic hyperplasia or BPH and prostate cancer. Symptoms of BPH affect between 50-70% of men over the age of 50 and prostate cancer is now the most common internal cancer diagnosed in men. More importantly, prostate cancer is the second most common cause of cancer deaths. We don't yet fully understand exactly how these diseases occur but the male sex hormones o ....Prostate disease is common in most men in later life and can affect their quality of life adversely. The primary conditions are benign prostatic hyperplasia or BPH and prostate cancer. Symptoms of BPH affect between 50-70% of men over the age of 50 and prostate cancer is now the most common internal cancer diagnosed in men. More importantly, prostate cancer is the second most common cause of cancer deaths. We don't yet fully understand exactly how these diseases occur but the male sex hormones or androgens are known to play an important role. Prostate specific antigen or PSA has become widely accepted as a useful tool in helping to detect prostate cancer and then monitoring the disease. PSA, which is regulated by androgens, is an enzyme that either activates or breaks down many proteins that are important in both the normal function of the prostate and in the development of cancer. PSA belongs to a family of enzymes called the kallikreins. We have recently discovered a new member of this family that, like PSA, is also found in the prostate. We have called this new enzyme, K6, as it is the sixth member of this family to be identified. So , this project is about characterising this new K6 enzyme, finding out if it is also found in the prostates of men with BPH and prostate cancer, whether it is also regulated by androgens and what sort of proteins it may activate in these diseases. We will also compare these findings with what we know about PSA in these diseases. From these studies, we will not only understand more about this K6 enzyme and how it might be important in the prostate but also how it relates to PSA. These findings may ultimately lead to some new approaches in the detection and treatment for BPH and prostate cancer.Read moreRead less
Harnessing Systems Biology By Integrating Proteomics And Immunopeptidomics To Understand Prostate Cancer Carcinogenesis, Diagnosis And Treatment
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
This ECF proposal aims to systematic profile to proteomic compositions of prostate normal, and cancer cells, and utilise such data to develop innovative systems biology models that will enable accurate prediction of tumour associate antigen (TAA) presentation for both aggressive and nonaggressive prostate cancer. The outcomes of this project will generate urgently needed knowledge for understanding TAA presentation and contribute to identification of tractable targets for vaccine development.
CHARACTERISATION AND ANTIBODY-MEDIATED TARGETING OF A NOVEL SPECIFIC MARKER FOR T CELL ALL/LYMPHOBLASTIC LYMPHOMA
Funder
National Health and Medical Research Council
Funding Amount
$586,146.00
Summary
Improvements in treatment have seen some types of leukaemia (a cancer of white blood cells) being curable in up to 90% of patients with the disease; however, other types of leukaemia do not respond to these drugs and new approaches are needed. We have discovered that some leukaemia cells express a unique protein not made by any other cell type. This project will analyse how this aberrant protein is made and how this process contributes to the development of leukaemia. Also, since this protein is ....Improvements in treatment have seen some types of leukaemia (a cancer of white blood cells) being curable in up to 90% of patients with the disease; however, other types of leukaemia do not respond to these drugs and new approaches are needed. We have discovered that some leukaemia cells express a unique protein not made by any other cell type. This project will analyse how this aberrant protein is made and how this process contributes to the development of leukaemia. Also, since this protein is unique to the leukaemia cells, it offers the opportunity to develop magic bullets able to target specifically to the leukaemia cells and to kill them. This project aims to make one such drug and to conduct preliminary testing.Read moreRead less
Immunopathogenesis Of Organ-specific Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$284,638.00
Summary
The immune system normally protects against invasion by pathogens such as harmful viruses and bacteria. In autoimmune diseases the same mechanisms that are used to protect us are erroneously targeted to our own tissues. Our studies will employ state-of-the art technologies to further our knowledge of this class of diseases and to uncover the normal mechanisms that allow the immune system to differentiate foreign and self components.
Intraprostatic Androgen Signalling As A Target In Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$372,049.00
Summary
Male hormones (androgens) are the fuel that drives prostate cancer so reducing androgen levels is the standard treatment but cant cure the disease and causes serious side-effects throughout the body. We need to better target androgen withdrawal to prostate cancers and learn more about how it works to improve treatment. This project utilizes unique mouse models for experiments not feasible in humans to learn how androgens act and can be better targeted to cure prostate cancers.