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
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.
Estrogen Therapy For Castrate Resistant Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$531,690.00
Summary
Withdrawal of male hormones in men with prostate cancer is effective therapeutically because it causes cell death in most of the tumour. However the remaining cells (called castrate resistant cells), give rise to recurrent disease that inevitably kills the patient. This project aims to test if our compound will kill these cells and prevent recurrence or if it has any benefit for the patients who have incurable disease.
Characterising The Beneficial Effects Of Estrogen On The Prostate Gland
Funder
National Health and Medical Research Council
Funding Amount
$594,722.00
Summary
Prostate cancer is hormonally regulated and currently managed by androgen ablation. This application seeks to study the potential benefits of estrogen action for the treatment of prostate disease, including PCa. We will show estrogen hormone action causes prostatic cell death, targeting the stem-progenitor cells so the treated prostatic tissue does not regenerate. This project will provide pre-clinical proof of the efficacy of estrogenic compounds as a potential therapy for prostate disease.
It has been recently found that some factors during intrauterine life are important and previously unsuspected determinants of cardiovascular disease decades later. The mechanisms are not yet clear but placental function in maintaining fetal nutrition and hormone secretion are likely to be important. Similar mechanisms have been found to affect female reproductive function and non-reproductive hormones in humans but the potential effects involving male reproductive health have not been studied s ....It has been recently found that some factors during intrauterine life are important and previously unsuspected determinants of cardiovascular disease decades later. The mechanisms are not yet clear but placental function in maintaining fetal nutrition and hormone secretion are likely to be important. Similar mechanisms have been found to affect female reproductive function and non-reproductive hormones in humans but the potential effects involving male reproductive health have not been studied so far. This project aims to search for prenatal factors that affect the development of the testis and prostate. By this means, prenatal factors may be an important in determining susceptibility to male infertility by lowering sperm output, androgen deficiency due to diminished testicular testosterone secretion and prostate disease notably prostatic hyperplasia. In this study we will employ our own specialised techniques for highly accurate measurement of the size of prostate zones and the testis using high frequency ultrasound. We will identify a birth cohort - a group of men born in a single hospital around 1970 - in whom we will measure prostate zones and testis size by ultrasound together with the hormonal markers relevant to the testis and prostate to examine whether any changes seen according to birthweight are due to concordant changes in hormones. This study could change the way in which disorders of male reproductive health are considered by focusing on factors occurring before and shortly after birth rather than on genetic or ambient environmntal factors in adult life which have been the overwhelming focus of research over recent decades.Read moreRead less