Lipocalin 2 in cancer: when good immunity goes bad.
Summary of "Lipocalin 2 in cancer: when good immunity goes bad."
The innate immune molecule Lipocalin 2 (LCN2) was initially shown to combat bacterial infection by binding bacterial siderophores, hence impairing microbial iron sequestration. In recent years, it has become apparent that LCN2 is over-expressed in cancers of diverse histological origin and that it facilitates tumorigenesis by promoting survival, growth, and metastasis. Herein, we discuss emerging evidence that substantiates two functional roles for LCN2 in cancer: promotion of the epithelial-to-mesenchymal transition (EMT) that facilitates an invasive phenotype and metastasis, and sequestration of iron that results in cell survival and tumorigenesis. Further, we present evidence that upregulated LCN2 expression in solid tumors is induced by hypoxia and pro-inflammation, microenvironmental noxae that converge to cause an endoplasmic reticulum (ER) stress response. Taken together, it appears that tumor cells exploit the beneficial innate immune function of LCN2 to support uncontrolled growth. This duplicity in function highlights LCN2 and its upstream driver, the ER stress response, as key targets for cancer therapy.
The Laboratory of Immunology, Department of Medicine and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093-0815, United States.
This article was published in the following journal.
Name: Cancer letters
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22075378
- DOI: http://dx.doi.org/10.1016/j.canlet.2011.11.002
Medical and Biotech [MESH] Definitions
A lipocalin that was orignally characterized from human TEARS. It is expressed primarily in the LACRIMAL GLAND and the VON EBNER GLANDS. Lipocalin 1 may play a role in olfactory transduction by concentrating and delivering odorants to the ODORANT RECEPTORS.
Testing of immune status in the diagnosis and therapy of cancer, immunoproliferative and immunodeficiency disorders, and autoimmune abnormalities. Changes in immune parameters are of special significance before, during and following organ transplantation. Strategies include measurement of tumor antigen and other markers (often by RADIOIMMUNOASSAY), studies of cellular or humoral immunity in cancer etiology, IMMUNOTHERAPY trials, etc.
Double Effect Principle
Guideline for determining when it is morally permissible to perform an action to pursue a good end with knowledge that the action will also bring about bad results. It generally states that, in cases where a contemplated action has such double effect, the action is permissible only if: it is not wrong in itself; the bad result is not intended; the good result is not a direct causal result of the bad result; and the good result is "proportionate to" the bad result. (from Solomon, "Double Effect," in Becker, The Encyclopedia of Ethics, 1992)
The non-susceptibility to infection of a large group of individuals in a population. A variety of factors can be responsible for herd immunity and this gives rise to the different definitions used in the literature. Most commonly, herd immunity refers to the case when, if most of the population is immune, infection of a single individual will not cause an epidemic. Also, in such immunized populations, susceptible individuals are not likely to become infected. Herd immunity can also refer to the case when unprotected individuals fail to contract a disease because the infecting organism has been banished from the population.
A cancer registry mandated under the National Cancer Act of 1971 to operate and maintain a population-based cancer reporting system, reporting periodically estimates of cancer incidence and mortality in the United States. The Surveillance, Epidemiology, and End Results (SEER) Program is a continuing project of the National Cancer Institute of the National Institutes of Health. Among its goals, in addition to assembling and reporting cancer statistics, are the monitoring of annual cancer incident trends and the promoting of studies designed to identify factors amenable to cancer control interventions. (From National Cancer Institute, NIH Publication No. 91-3074, October 1990)
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