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Gene activity reveals dynamic stroma microenvironment in prostate cancer
June 09, 2009As stroma - the supportive framework of the prostate gland - react to prostate cancer, changes in the expression of genes occur that induce the formation of new structures such as blood vessels, nerves and parts of nerves, said researchers at Baylor College of Medicine in a report that appears in the current issue of the journal Clinical Cancer Research.
In this study, using special techniques and gene chips that allowed them to sample the entire genome, the researchers found changes in 1,141 genes. They were either upregulated - meaning that there was more of the protein with which they were associated than expected - or downregulated, which meant the opposite, said Dr. Michael Ittmann, professor of pathology at BCM and a senior author of the report. These gene changes may explain why men with reactive stroma face a more aggressive disease, said Ittmann and Dr. Gustavo Ayala, professor in the departments of pathology and urology at BCM and another senior author.
"Often in prostate cancer, you don't see much change in the stromal cells," said Ittmann. "However, in this subgroup of patients (in which the stroma become visibly reactive), you see a histologically recognizable change in the appearance of the stroma. Dr. Ayala has shown previously that this correlates with a bad prognosis. We know the stroma are doing something to promote bad behavior in cancer cells."
"These findings are very important as this is the first step in discovering pathways and mechanisms in the tumor microenvironment that could be targeted as a novel therapeutic approach to treat prostate cancer by treating the cancer microenvironment niche", said Dr. David Rowley, professor of molecular and cellular biology and urology at BCM, and another author.
Dr. Chad Creighton, an assistant professor in the Dan L. Duncan Cancer Center at BCM, searched the scientific literature to determine the biological processes with which the genes with changes had been linked in prior studies.
"We found that the top terms linked to the genes were related to neurogenesis (the growth of neurons or nerve cells)," said Ittmann. "This independently supported Dr. Ayala's previous finding that prostate cancer prompts the growth of new nerve cells, which is linked to poor prognosis."
Other genes were linked to axongenesis, which refers to new axons, the slender projection that conducts nerve impulses away from the body of a nerve cell.
That finding was exciting because it confirmed the neurogenesis findings from a new direction, said Ittmann and Ayala.
"We also found many changes in the DNA damage pathway genes," Ittmann said. These genes reduce the negative effects of DNA changes on cells - either by correcting the DNA or prompting cell death. "This implies that there may be different kinds of DNA damaging stimuli going on in the stroma as well as cancer cells," said Ittmann. "DNA damage could be related to mutations in the stroma."
The researchers also found changes in growth factor pathways, including those for fibroblast growth factor and transforming growth factor beta as well as pathways linked to the growth and maintenance of stem cells, said Ittmann.
While many of the gene changes they found may have no role in prostate cancer, the report lays the groundwork for determining which players and processes may have a role, he said.
"One question is what are the pathways turning on some of these genes in response to signals from the cancer cells," he said. "This description is the start," said Ittmann. "Now we can work on the mechanisms."
"We know that of all men who get prostate cancer, only about 10 percent would die of it," he said. "Of those who have disease localized to the prostate gland, only 5 percent would die from the disease. How do we differentiate those who really need treatment from those who might not? Can we identify the biomarkers that differentiate those? There is probably more than one marker and some may be stromal-based."
Baylor College of Medicine
"These findings are very important as this is the first step in discovering pathways and mechanisms in the tumor microenvironment that could be targeted as a novel therapeutic approach to treat prostate cancer by treating the cancer microenvironment niche", said Dr. David Rowley, professor of molecular and cellular biology and urology at BCM, and another author.
Dr. Chad Creighton, an assistant professor in the Dan L. Duncan Cancer Center at BCM, searched the scientific literature to determine the biological processes with which the genes with changes had been linked in prior studies.
"We found that the top terms linked to the genes were related to neurogenesis (the growth of neurons or nerve cells)," said Ittmann. "This independently supported Dr. Ayala's previous finding that prostate cancer prompts the growth of new nerve cells, which is linked to poor prognosis."
Other genes were linked to axongenesis, which refers to new axons, the slender projection that conducts nerve impulses away from the body of a nerve cell.
That finding was exciting because it confirmed the neurogenesis findings from a new direction, said Ittmann and Ayala.
"We also found many changes in the DNA damage pathway genes," Ittmann said. These genes reduce the negative effects of DNA changes on cells - either by correcting the DNA or prompting cell death. "This implies that there may be different kinds of DNA damaging stimuli going on in the stroma as well as cancer cells," said Ittmann. "DNA damage could be related to mutations in the stroma."
The researchers also found changes in growth factor pathways, including those for fibroblast growth factor and transforming growth factor beta as well as pathways linked to the growth and maintenance of stem cells, said Ittmann.
While many of the gene changes they found may have no role in prostate cancer, the report lays the groundwork for determining which players and processes may have a role, he said.
"One question is what are the pathways turning on some of these genes in response to signals from the cancer cells," he said. "This description is the start," said Ittmann. "Now we can work on the mechanisms."
"We know that of all men who get prostate cancer, only about 10 percent would die of it," he said. "Of those who have disease localized to the prostate gland, only 5 percent would die from the disease. How do we differentiate those who really need treatment from those who might not? Can we identify the biomarkers that differentiate those? There is probably more than one marker and some may be stromal-based."
Baylor College of Medicine
Prostate Cancer Current Events and Prostate Cancer News RSSCarnegie Mellon researchers link health-care debate to risk of dying in US and Europe
The current health care debate in the United States is complicated. Trade-offs between heath care expenditures, lifestyle choices and life expectancy have been suggested but seldom clearly demonstrated.
New finding suggests prostate biopsy is not always necessary
Researchers at Wake Forest University School of Medicine and the University of Wisconsin-Madison have discovered that some elevated prostate-specific antigen (PSA) levels in men may be caused by a hormone normally occurring in the body, and are not necessarily a predictor of the need for a prostate biopsy.
Does prostate-specific antigen velocity help in early detection prostate cancer?
The November issue of European Urology, the official journal of the European Association of Urology, features an article focussing on prostate specific antigen (PSA) velocity and early cancer detection. It has been suggested that changes in PSA over time aid prostate cancer detection.
New Synthetic Molecules Trigger Immune Response to HIV and Prostate Cancer
Researchers at Yale University have developed synthetic molecules capable of enhancing the body's immune response to HIV and HIV-infected cells, as well as to prostate cancer cells. Their findings, published online in the Journal of the American Chemical Society, could lead to novel therapeutic approaches for these diseases.
Chemo-radiation before prostate removal may prevent cancer recurrence
Researchers in the Oregon Health & Science University Knight Cancer Institute and the Portland Veterans Affairs Medical Center have found a combination of radiation therapy and chemotherapy given before prostate removal is safe and may have the potential to reduce cancer recurrence and improve patient survival.
Blood vessels might predict prostate cancer behavior
A diagnosis of prostate cancer raises the question for patients and their physicians as to how the tumor will behave. Will it grow quickly and aggressively and require continuous treatment, or slowly, allowing therapy and its risks to be safely delayed?
Short-term hormone therapy and intermediate dose radiation increases survivial for early stage prostate cancer
Short-term hormone therapy given prior to and during intermediate dose radiation treatment for men with early stage prostate cancer increases their chance of living longer, compared to those who receive the same radiation alone.
Task force develops new radiation guidelines for brachytherapy
Radiation dose delivered to the prostate and nearby organs in every brachytherapy procedure should be carefully analyzed using post-implant CT or MRI and uniformly documented in every patient.
1 disease, not 1 demographic
The Asian continent has nearly four billion people living in 47 different countries, and each of these groups has their own unique set of health issues. But when they come to the United States, they're often lumped into one large demographic: "Asian/Pacific Islander."
Cancer survivors may not be getting the help they need to stop smoking
More than a quarter of cancer survivors who still smoke have not been advised to quit smoking by their health care providers in the last year, according to a study published by researchers at Fox Chase Cancer Center in the current issue of the Journal of General Internal Medicine.
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