骨髓促进肿瘤血管生成
WESTPORT, CT (Reuters Health) - Bone marrow-derived endothelial and hematopoietic stem cells are critical for tumor angiogenesis in mice, according to a report published Wednesday in the November issue of Nature Medicine.
"The question has been what is the origin of the endothelial cells that are recruited to the tumor vascular bed that enable tumor growth," Dr. Shahin Rafii from Cornell University Medical College, New York, told Reuters Health. The prevailing theory has been that these are local endothelial cells, he noted.
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"But what we show is that in addition to the recruitment of local cells, tumor cells have the capacity to send signals to the bone marrow and to recruit endothelial and hematopoietic precursor cells from the bone marrow to the tumor. Not only does this define the mechanism of tumor growth, but it also provides novel targets for therapy," Dr. Rafii said.
The researchers transplanted bone marrow cells from wild-type mice into mice that were deficient in Id1 and null for Id3, two proteins essential for tumor angiogenesis. They then inoculated the mice with lymphoma or lung carcinoma cells. "To our surprise the tumor started to grow" in the mutant mice, Dr. Rafii said. The growth paralleled that observed in the wild-type animals.
, 百拇医药
In an extension of the same experiment, the bone marrow cells from wild-type mice were labeled with a genetic mark. The researchers observed cells with the genetic mark in practically all of the vessels that formed in tumors in Id-deficient mice, which suggests that they came from the bone marrow, Dr. Rafii said.
The precursor cells are mobilized and recruited by vascular endothelial growth factor (VEGF) stem cells, he added, explaining that when his team used antibodies to block both VEGF receptor-1 and -2, tumor growth was halted in the mice.
, http://www.100md.com
"If we can find and catalog tumors that are bone marrow-dependent we may be able to target specific factors in the bone marrow to prevent tumor growth," Dr. Rafii said. "This could reduce the toxicity of chemotherapy and be more efficacious."
He said that another strategy would be to harvest the stem cells, load them with a toxin and reinfuse them into the patient. "These stem cells would be a biological cruise missile and home in on the tumor vascular bed, releasing their load and killing the tumor," he said.
, 百拇医药
In a separate interview with Reuters Health, coauthor Dr. Robert Benezra from Memorial Sloan-Kettering Cancer Center, in New York, suggested that "monitoring these cells may be a potential diagnostic for minimal residual disease, because these cells come out of the bone marrow very early in tumor genesis."
Nature Med 2001;7:1194-1201.
-Westport Newsroom 203 319 2700
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"The question has been what is the origin of the endothelial cells that are recruited to the tumor vascular bed that enable tumor growth," Dr. Shahin Rafii from Cornell University Medical College, New York, told Reuters Health. The prevailing theory has been that these are local endothelial cells, he noted.
, http://www.100md.com
"But what we show is that in addition to the recruitment of local cells, tumor cells have the capacity to send signals to the bone marrow and to recruit endothelial and hematopoietic precursor cells from the bone marrow to the tumor. Not only does this define the mechanism of tumor growth, but it also provides novel targets for therapy," Dr. Rafii said.
The researchers transplanted bone marrow cells from wild-type mice into mice that were deficient in Id1 and null for Id3, two proteins essential for tumor angiogenesis. They then inoculated the mice with lymphoma or lung carcinoma cells. "To our surprise the tumor started to grow" in the mutant mice, Dr. Rafii said. The growth paralleled that observed in the wild-type animals.
, 百拇医药
In an extension of the same experiment, the bone marrow cells from wild-type mice were labeled with a genetic mark. The researchers observed cells with the genetic mark in practically all of the vessels that formed in tumors in Id-deficient mice, which suggests that they came from the bone marrow, Dr. Rafii said.
The precursor cells are mobilized and recruited by vascular endothelial growth factor (VEGF) stem cells, he added, explaining that when his team used antibodies to block both VEGF receptor-1 and -2, tumor growth was halted in the mice.
, http://www.100md.com
"If we can find and catalog tumors that are bone marrow-dependent we may be able to target specific factors in the bone marrow to prevent tumor growth," Dr. Rafii said. "This could reduce the toxicity of chemotherapy and be more efficacious."
He said that another strategy would be to harvest the stem cells, load them with a toxin and reinfuse them into the patient. "These stem cells would be a biological cruise missile and home in on the tumor vascular bed, releasing their load and killing the tumor," he said.
, 百拇医药
In a separate interview with Reuters Health, coauthor Dr. Robert Benezra from Memorial Sloan-Kettering Cancer Center, in New York, suggested that "monitoring these cells may be a potential diagnostic for minimal residual disease, because these cells come out of the bone marrow very early in tumor genesis."
Nature Med 2001;7:1194-1201.
-Westport Newsroom 203 319 2700
Exception:java.sql.SQLException: Connection has already been closed., http://www.100md.com