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Wound-healing genes promote cancer progression
Newsdesk
The same mechanisms that play an essential part in normal wound healing may promote the progression of many common cancers, says a new study published in PLoS Biology (doi: 10.1371 /journal.pbio.0020007). It has long been recognised that carcinoma cells and their surrounding stroma behave in a remarkably similar way to cells in a healing wound with characterisitics such as rapid division, migration, remodelling and invasion of connective tissue, and an ability to induce angiogenesis. In 1986, Harold Dvorak (Beth Israel Deaconess Medical Center, Boston, MA, USA) made the most graphic analogy between wound healing and cancer when he said that tumours are wounds that do not heal. However, until now, the relation between both processes had never been evaluated at the molecular level. But researchers at Stanford University, CA, USA, noted that many genes expressed during wound healing are also active in cancer. This observation lead to a systematic analysis of publically available microarray data of tumour cells and their stroma and a comparison with the gene expression programme activated in fibroblasts exposed to serum. “We knew from our previous work...that this seemed to be a very good laboratory model in which to study the molecular physiology of wound healing,” says Patrick Brown, senior author of the Stanford study. The comparison confirmed that the patterns of gene expression in wounds and some tumours are similar. “It suggests that the way that tumours acquire the ability to create complex tissues does not involve their de novo invention of the complex programme of stromal activation”, comments Robert Weinberg at the Whitehead Institute for Biomedical Research (Cambridge, MA, USA). “Instead, they activate a latent, pre-existing woundhealing programme that is encoded in the normal genome, which they then use as the strategy for constructing their own stroma.” The investigators found that liver and prostate cancers always activated genes involved in wound healing. In
138
Courtesy of Patrick Brown
Wound-healing genes promote cancer progression
Wound healing and cancer have key similarities.
other tumours, such as breast, lung, and gastric cancer, the wound-like genetic signature was not always present—but when it was, it correlated with a higher risk of cancer progression
and death. Based on this observation, Brown and colleagues are now developing simple immunohistochemical assays that would recognise the wound-like signature and allow oncologists to identify patients with aggressive cancers, so they can make better treatment decisions. Further research may also help identify genes expressed in the stroma that are important for cancer-cell proliferation. The Stanford team has already begun elucidating the molecular signalling pathways that seem to be involved in the serum-response programme, wound healing, and cancer. “We are testing some ideas for chemical inhibitors of the programme”, hints Brown. Martina Habeck
ALL and type-1 diabetes link Countries with a high incidence of acute lymphoblastic leukaemia (ALL) also have high incidence of type-1 diabetes, a new study shows (Arch Dis Child 2004; 89: 54–56). “Our results are compatible with the hypothesis that exposure to infections in early life reduces the risk of future development of ALL and diabetes in childhood”, extrapolates lead author Richard Feltbower (University of Leeds, UK). The incidence of ALL and type-1 diabetes has increased in many affluent countries over the past 20 years. Studying data from 40 countries, Feltbower and colleagues investigated whether a correlation existed between the incidence of both diseases in children <14 years of age, and whether there were any underlying factors explaining variance between countries. They authors found a significant correlation between ALL and type-1 diabetes (r=0·53). However, they caution that their findings do not imply that being diagnosed with one condition automatically increases an individual’s risk of developing the other condition. They also found that a high incidence of both ALL and
diabetes was significantly associated with extent of national prosperity. Richard McNally (University of Manchester, UK) believes these findings are important because they are the first to provide evidence that there is an ecological correlation between the incidence of ALL and type-I diabetes in children, using international data. “The findings are are the first to show that the incidence of both ALL and type-I diabetes in children are correlated with measures of national prosperity. Previous studies have only looked within countries or parts of countries”, McNally comments. According to Edwin Gale (Southmead Hospital, Bristol, UK), this preliminary observation is very interesting and now needs to be followed-up with further studies: “Childhood diabetes, for example, correlates very well with many markers of affluence [and this] study provides further ecological evidence that both childhood ALL and type-I diabetes share a common aetiological mechanism, which is likely to involve delayed exposure to infectious agents”, remarks Gale. Khabir Ahmad
THE LANCET Oncology Vol 5 March 2004
For personal use. Only reproduce with permission from The Lancet.
http://oncology.thelancet.com
The same mechanisms that play an essential part in normal wound healing may promote the progression of many common cancers, says a new study published in PLoS Biology (doi: 10.1371 /journal.pbio.0020007). It has long been recognised that carcinoma cells and their surrounding stroma behave in a remarkably similar way to cells in a healing wound with characterisitics such as rapid division, migration, remodelling and invasion of connective tissue, and an ability to induce angiogenesis. In 1986, Harold Dvorak (Beth Israel Deaconess Medical Center, Boston, MA, USA) made the most graphic analogy between wound healing and cancer when he said that tumours are wounds that do not heal. However, until now, the relation between both processes had never been evaluated at the molecular level. But researchers at Stanford University, CA, USA, noted that many genes expressed during wound healing are also active in cancer. This observation lead to a systematic analysis of publically available microarray data of tumour cells and their stroma and a comparison with the gene expression programme activated in fibroblasts exposed to serum. “We knew from our previous work...that this seemed to be a very good laboratory model in which to study the molecular physiology of wound healing,” says Patrick Brown, senior author of the Stanford study. The comparison confirmed that the patterns of gene expression in wounds and some tumours are similar. “It suggests that the way that tumours acquire the ability to create complex tissues does not involve their de novo invention of the complex programme of stromal activation”, comments Robert Weinberg at the Whitehead Institute for Biomedical Research (Cambridge, MA, USA). “Instead, they activate a latent, pre-existing woundhealing programme that is encoded in the normal genome, which they then use as the strategy for constructing their own stroma.” The investigators found that liver and prostate cancers always activated genes involved in wound healing. In
138
Courtesy of Patrick Brown
Wound-healing genes promote cancer progression
Wound healing and cancer have key similarities.
other tumours, such as breast, lung, and gastric cancer, the wound-like genetic signature was not always present—but when it was, it correlated with a higher risk of cancer progression
and death. Based on this observation, Brown and colleagues are now developing simple immunohistochemical assays that would recognise the wound-like signature and allow oncologists to identify patients with aggressive cancers, so they can make better treatment decisions. Further research may also help identify genes expressed in the stroma that are important for cancer-cell proliferation. The Stanford team has already begun elucidating the molecular signalling pathways that seem to be involved in the serum-response programme, wound healing, and cancer. “We are testing some ideas for chemical inhibitors of the programme”, hints Brown. Martina Habeck
ALL and type-1 diabetes link Countries with a high incidence of acute lymphoblastic leukaemia (ALL) also have high incidence of type-1 diabetes, a new study shows (Arch Dis Child 2004; 89: 54–56). “Our results are compatible with the hypothesis that exposure to infections in early life reduces the risk of future development of ALL and diabetes in childhood”, extrapolates lead author Richard Feltbower (University of Leeds, UK). The incidence of ALL and type-1 diabetes has increased in many affluent countries over the past 20 years. Studying data from 40 countries, Feltbower and colleagues investigated whether a correlation existed between the incidence of both diseases in children <14 years of age, and whether there were any underlying factors explaining variance between countries. They authors found a significant correlation between ALL and type-1 diabetes (r=0·53). However, they caution that their findings do not imply that being diagnosed with one condition automatically increases an individual’s risk of developing the other condition. They also found that a high incidence of both ALL and
diabetes was significantly associated with extent of national prosperity. Richard McNally (University of Manchester, UK) believes these findings are important because they are the first to provide evidence that there is an ecological correlation between the incidence of ALL and type-I diabetes in children, using international data. “The findings are are the first to show that the incidence of both ALL and type-I diabetes in children are correlated with measures of national prosperity. Previous studies have only looked within countries or parts of countries”, McNally comments. According to Edwin Gale (Southmead Hospital, Bristol, UK), this preliminary observation is very interesting and now needs to be followed-up with further studies: “Childhood diabetes, for example, correlates very well with many markers of affluence [and this] study provides further ecological evidence that both childhood ALL and type-I diabetes share a common aetiological mechanism, which is likely to involve delayed exposure to infectious agents”, remarks Gale. Khabir Ahmad
THE LANCET Oncology Vol 5 March 2004
For personal use. Only reproduce with permission from The Lancet.
http://oncology.thelancet.com