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A potential inhibitor of metastasis?
Newsdesk
US researchers are hopeful that a drug therapy targeting the human protein galectin 3 may inhibit the spread of breast cancer, after finding that a modified form of the protein successfully reduced metastasis and tumour size in a human breast-cancer model (Clin Cancer Res 2003; 9: 2374–83). Mounting evidence implicates galectin 3 in several tumour-relevant processes including growth, differentiation, adhesion, RNA processing, apoptosis, and malignant transformation. Using this knowledge, researchers from San Francisco VA Medical Center, CA, USA, hypothesised that an NH2 truncated form of galectin 3 (galectin 3C) could inhibit tumorigenicity, invasion, and metastasis. They tested this theory in nude mice implanted with human breast cancer cells and found that the cancer spread to lymph nodes and other organs in four of 20 mice treated with galectin 3C, compared with 11 of 20 control mice—a decrease of 275%. Tumour growth was also substantially less in treated animals and, even at the highest doses, the modified protein was well tolerated. “Our results provide compelling evidence that galectin 3C could be useful in the treatment and prevention of metastatic breast cancer”, the researchers conclude. Senior-author Gary Jarvis, believes it is the first time the modified protein has been tested as a therapeutic agent for cancer, and says the study has since been repeated with nearly identical results. “We are confident of our findings and our conclusions”, he says. It was initially thought that the modified protein may compete with endogenous galectin 3 for both intracellular and extracellular carbohydrate binding sites, explains Jarvis, but research is continuing into the mechanism behind the observed reduction in metastasis. The team are also planning to study the use of galectin 3C for treating other cancers such as prostate and colon cancer. “If we can stop metastasis in humans, we will have gone a long way towards curing cancer”, he adds. Alan Coates, chairman of the
390
Rights were not granted to include this image in electronic media. Please refer to the printed journal. Breast cancer cells.
scientific advisory committee of the Australia and New Zealand Breast Cancer Trials Group, says it had been recognised for several decades that carbohydrates on cell surfaces played
Cecil H Fox/Science Photo Library
A potential inhibitor of metastasis? some role in cancer metastasis.“It is entirely plausible that changes on the outside of the cell will affect its metastatic potential”, he comments. However, Coates points out that it is too early to draw conclusions about the potential benefits of truncated galectin 3 therapy, since the study results on tumour growth were not overly impressive. Despite the researchers’ enthusiasm, Coates remains sceptical. “This work may hint at a principle that might be effective”, he says. “But I would not hold my breath to see it in the clinic.” Megan Howe
Depression may increase cancer risk Studies of anxiety and depression in patients with cancer generally focus on diagnosing psychological illness. But could psychological illness actually cause cancer? Two new studies that link psychological disorders with immune dysfunction suggest it might. To identify associations between mental health and cancer, Arnstein Mykletun (University of Bergen, Norway) and colleagues measured anxiety and depression in a large population study in Nord-Trøndelag County, Norway, from 1995 to 1997. They also retrieved information about cancer incidence among this group by using the country’s National Cancer Registry. They found that of the 62 591 participants, 2161 developed cancer during the follow-up period, and an additional 849 individuals developed premalignant lesions. Controlling for confounding factors such as presence of previous cancer, age, and gender, they concluded that a “diagnosis of anxiety and depression was predictive of premalignancies, but not malignant diagnoses”, says Mykletun. But, he adds, “more study is needed before anxiety and depression are classified as risk-factors for cancer”. In another investigation, Edna Reiche and colleagues (State University of Londrina, Brazil) studied 40 non-medicated, depressed adults and 34 healthy non-depressed compar-
isons and found that their immune and hormonal measurements differed significantly (Braz J Med Biol Res 2002; 35: 581–87). In depressed patients, lymphocyte proliferation in response to a mitogen was significantly lower than in controls. “The impaired cellular immune response could decrease production of cytokines that have an important role in activating NK cells”, explains Reiche. Very seriously depressed individuals had substantially reduced serum albumin concentrations and unusually high amounts of positive acute-phase protein. “Psychological stress, not only infectious challenges, can cause release of hormones and proinflammatory cytokines, and trigger behavioural and immunological changes”, says Reiche. But, rather than insinuating a direct association between the mind and cancer, Christoffer Johansen of the Danish Cancer Society (Copenhagen, Denmark), believes depression may predispose individuals to behaviour that puts them at higher cancer risk. “In a cohort of 90 000 clinically depressed, hospitalised patients, we found an increased risk for smoking and alcohol-related cancers”, says Johansen. But, he adds, “No clear answers have been found yet”. Kathleen Nelson
THE LANCET Oncology Vol 4 July 2003
For personal use. Only reproduce with permission from The Lancet.
http://oncology.thelancet.com
US researchers are hopeful that a drug therapy targeting the human protein galectin 3 may inhibit the spread of breast cancer, after finding that a modified form of the protein successfully reduced metastasis and tumour size in a human breast-cancer model (Clin Cancer Res 2003; 9: 2374–83). Mounting evidence implicates galectin 3 in several tumour-relevant processes including growth, differentiation, adhesion, RNA processing, apoptosis, and malignant transformation. Using this knowledge, researchers from San Francisco VA Medical Center, CA, USA, hypothesised that an NH2 truncated form of galectin 3 (galectin 3C) could inhibit tumorigenicity, invasion, and metastasis. They tested this theory in nude mice implanted with human breast cancer cells and found that the cancer spread to lymph nodes and other organs in four of 20 mice treated with galectin 3C, compared with 11 of 20 control mice—a decrease of 275%. Tumour growth was also substantially less in treated animals and, even at the highest doses, the modified protein was well tolerated. “Our results provide compelling evidence that galectin 3C could be useful in the treatment and prevention of metastatic breast cancer”, the researchers conclude. Senior-author Gary Jarvis, believes it is the first time the modified protein has been tested as a therapeutic agent for cancer, and says the study has since been repeated with nearly identical results. “We are confident of our findings and our conclusions”, he says. It was initially thought that the modified protein may compete with endogenous galectin 3 for both intracellular and extracellular carbohydrate binding sites, explains Jarvis, but research is continuing into the mechanism behind the observed reduction in metastasis. The team are also planning to study the use of galectin 3C for treating other cancers such as prostate and colon cancer. “If we can stop metastasis in humans, we will have gone a long way towards curing cancer”, he adds. Alan Coates, chairman of the
390
Rights were not granted to include this image in electronic media. Please refer to the printed journal. Breast cancer cells.
scientific advisory committee of the Australia and New Zealand Breast Cancer Trials Group, says it had been recognised for several decades that carbohydrates on cell surfaces played
Cecil H Fox/Science Photo Library
A potential inhibitor of metastasis? some role in cancer metastasis.“It is entirely plausible that changes on the outside of the cell will affect its metastatic potential”, he comments. However, Coates points out that it is too early to draw conclusions about the potential benefits of truncated galectin 3 therapy, since the study results on tumour growth were not overly impressive. Despite the researchers’ enthusiasm, Coates remains sceptical. “This work may hint at a principle that might be effective”, he says. “But I would not hold my breath to see it in the clinic.” Megan Howe
Depression may increase cancer risk Studies of anxiety and depression in patients with cancer generally focus on diagnosing psychological illness. But could psychological illness actually cause cancer? Two new studies that link psychological disorders with immune dysfunction suggest it might. To identify associations between mental health and cancer, Arnstein Mykletun (University of Bergen, Norway) and colleagues measured anxiety and depression in a large population study in Nord-Trøndelag County, Norway, from 1995 to 1997. They also retrieved information about cancer incidence among this group by using the country’s National Cancer Registry. They found that of the 62 591 participants, 2161 developed cancer during the follow-up period, and an additional 849 individuals developed premalignant lesions. Controlling for confounding factors such as presence of previous cancer, age, and gender, they concluded that a “diagnosis of anxiety and depression was predictive of premalignancies, but not malignant diagnoses”, says Mykletun. But, he adds, “more study is needed before anxiety and depression are classified as risk-factors for cancer”. In another investigation, Edna Reiche and colleagues (State University of Londrina, Brazil) studied 40 non-medicated, depressed adults and 34 healthy non-depressed compar-
isons and found that their immune and hormonal measurements differed significantly (Braz J Med Biol Res 2002; 35: 581–87). In depressed patients, lymphocyte proliferation in response to a mitogen was significantly lower than in controls. “The impaired cellular immune response could decrease production of cytokines that have an important role in activating NK cells”, explains Reiche. Very seriously depressed individuals had substantially reduced serum albumin concentrations and unusually high amounts of positive acute-phase protein. “Psychological stress, not only infectious challenges, can cause release of hormones and proinflammatory cytokines, and trigger behavioural and immunological changes”, says Reiche. But, rather than insinuating a direct association between the mind and cancer, Christoffer Johansen of the Danish Cancer Society (Copenhagen, Denmark), believes depression may predispose individuals to behaviour that puts them at higher cancer risk. “In a cohort of 90 000 clinically depressed, hospitalised patients, we found an increased risk for smoking and alcohol-related cancers”, says Johansen. But, he adds, “No clear answers have been found yet”. Kathleen Nelson
THE LANCET Oncology Vol 4 July 2003
For personal use. Only reproduce with permission from The Lancet.
http://oncology.thelancet.com