New tissue grafts will help study cancer's causes!
Human breasts grown on mice
New tissue grafts will help study cancer's causes.
23 March 2004
Healthy human fibroblast tissue from a mouse.
Lab mice have grown tissue more usually confined to a bra - lumps of human breast. The growths should help researchers work out how cancer develops.
Researchers commonly use genetically engineered mice to study cancer, but the animal disease differs slightly from the human one. So researchers have sought to transplant human breast tissue into mice to make a better model.
Now Robert Weinberg of the Whitehead Institute for Biomedical Research in Boston and his team have succeeded. They report their method in the Proceedings of the National Academy of Sciences1.
The key, Weinberg says, is to transplant two types of human breast cells into the mice, one of which has been blasted with radiation.
The cells grow into human-like breast tissues, complete with milk ducts. Unlike human breasts, however, the mice's growths sit flush to the chest. Humans are unusual in this respect, says Daniel Medina who studies breast cancer at Baylor College of Medicine at Houston, Texas: "In few other species are breasts pendulous."
In the past, some researchers transplanted only one type of breast cell, called epithelial cells, into mice. These cells line the milk ducts, and are where breast cancers start. But such attempts were "doomed to failure", says Weinberg, because they lacked a second element of human breast tissue - support cells called fibroblasts.
So Weinberg's team took fibroblast tissue from women who had undergone breast reduction surgery. They blasted half the fibroblasts with X-rays, injected both healthy and irradiated cells into mouse mammary glands, and grafted human epithelial breast cells alongside.
Weinberg thinks that irradiating the fibroblasts helps the epithelial cells survive. He is not sure how it works, but it may provoke an inflammatory response that helps to protect the cells. "It's hocus-pocus," he says.
The human-breasted mice also develop cancer in much the same way as humans. Scientists think breast cancer starts when one epithelial cell gets a mutation in its DNA and starts dividing wildly into a tumour.
When the team modified the human fibroblasts so that they made a protein often over-produced in human breast tumours, the mice developed cancer in their epithelia.
This suggests that the transplanted epithelial cells were harbouring mutations that turned cancerous in response to signals from neighbouring cells. Researchers hope the new system will help them tease out these signals and, perhaps, find ways to stall them. "It's a very big advance," says Medina.
Kuperwasser, C. et al. Proc. Natl. Acad. Sci., published online, doi:10.1073/pnas.0401064101 (2004). |Article| 看过相关的文章，有一名词"tumor associated fibroblast"，就是研究肿瘤间质内成纤维细胞和肿瘤细胞的相互作用。肿瘤的微环境（包括临近细胞、细胞因子等）对肿瘤进展的作用已日益引起人们的关注。
review about "tumor associated fibroblast":
作者:admin@医学,生命科学 2011-02-19 17:11