How primary tumours prepare lung for invasion – Nature Cell Biology
Loss of a key enzyme can substantially alter how the immune system recognizes tissue antigens according to a report in the January issue of Nature Immunology.Nilabh Shastri and colleagues took a close look at mice lacking the enzyme called ERAAP, to discover if these mice bore any immunologic defect. ERAAP trims bits of protein that are displayed on cell surfaces by molecules known as major histocompatibility antigens (MHC), which are the tissue-matching antigens doctors use to identify potential organ donors for transplant patients. Essentially, this trimming process is akin to fitting an oversized hot dog into a bun; ERAAP clips the protruding end of the peptide to nestle snugly within the confines of the MHC molecule.The study shows vigorous immune reactions resulted when researchers mixed cells from ERAAP-deficient mice with those of wild-type mice that express ERAAP protein. These immune responses were as strong as those seen during rejection episodes of MHC-mismatched transplant patients. These results suggest vast differences exist in the collection of peptides presented by the ERAAP-deficient cells as compared to otherwise genetically identical wild-type mice. The authors speculate inhibiting ERAAP function in tumours might enhance their ability to be targeted and destroyed by the immune system, or conversely, spontaneous loss of ERAAP function in otherwise healthy tissues might lead to autoimmune disease.
Primary tumours prepare the lung for invasion by inducing factors that guide migration of both inflammatory and tumour cells to the lung according to a study in the December issue of Nature Cell Biology.Many solid tumours develop through a process of metastasis, where the cancer spreads from the primary site to other places in the body. Metastasis reduces both the chances of treatment and underlies late stage symptoms, yet research into the process is in its infancy.Sachie Hiratsuka and colleagues studied tumour-bearing mice and found that certain proteins called chemokines are induced in the lung by a set of factors secreted by the primary tumour. The chemokines induce migration of both inflammatory and tumour cells to the lung. An amplifying circuit is created between the primary tumour and the premetastatic tissue to facilitate metastatic tumour invasion. Interrupting this circuit of signals between the primary tumour and cells in the lung efficiently blocked lung metastases in mice. Blocking migration of tumour cells to the metastatic sites at an early stage presents a promising clinical avenue to prevent the spread of cancer.
A new technique for analyzing bacterial genetic information is outlined in the January issue of Nature Methods, opening the door for a comprehensive study of all bacteria in our guts. The technique allows researchers to capture and analyze the genetic hitchhikers of the bacterial world – small bits of bacterial genetic information that usually escape scrutiny.For many organisms once the genome is sequenced all the information needed to determine functionally important genes becomes available. This is not the case for bacteria however. Many bacteria possess hitchhiker genes in the form of small circular DNA molecules called plasmids. Not only do the plasmids contain genes that provide new abilities to the bacteria but copies of these plasmids can also be transferred to other bacteria.Most large-scale sequencing efforts to characterize all the microorganisms in an ecosystem are unsuitable for analyzing the complex population of plasmids that provides extra-genomic genes. Julian Marchesi and colleagues describe a method to selectively capture these bacterial hitchhikers so they can be sequenced. They tested their method on the bacterial ecosystem living in the human gut and discovered plasmids containing genes of known and unknown function. This method should help determine just how important these small hitchhikers are and what effect they have on microbial ecosystems.