Some malignant human tumors cells also express FPRs and

Some malignant human tumors formyl peptide receptors also express FPRs and respond to bacterial or endogenous agonists by increased motility and growth. For instance, FPRs expressed by human gastric cancer cells, mediate epithelial–mesenchymal transition, cell proliferation, migration, and resistance to apoptosis [30]. The prototype FPR, FPR1, selectively expressed by highly malignant glioblastoma multiforme (GBM) cells, responds to an endogenous chemotactic ligand anexin 1 (ANXA1) released by necrotic GBM cells [31]. Activated FPR1 cooperates with the epidermal growth factor receptor (EGFR) to enhance the survival, invasiveness, and production of antigenic factors by GBM cells [2], [32], [33], [34], [35]. Human breast cancer cells also express FPR1 and FPR2, which interact with a shared ligand ANXA1 to enhance tumor cell proliferation [36]. In human liver cancer cells, FPR1 was implicated in promoting cell invasion, proliferation, and production of angiogenic factors [2]. A recent study shows that FPR2 is utilized by human colon cancer cells for their growth advantage [37]. Thus, FPRs are suggested to be hijacked by tumor cells for their benefits. In addition to their expression in diverse cell types, FPRs are notorious for ligand promiscuity, by interacting with both pathogen-associated chemotactic molecular patterns (PAMPs) and damage-associated chemotactic molecular patterns (DAMPs). During the past few years, with the availability of genetically engineered mouse strains deficient in one or more Fprs, the critical roles of FPRs (Fprs) in disease progression are increasingly recognized [38]. A lot of studies revealed that FPRs not only mediate leukocyte trafficking but also promote myeloid cell differentiation, colon epithelial homeostasis, and cancer progression. Therefore, a better understanding of the biologic significance of FPRs (Fprs) should have important clinical relevance. This review will focus on the role of FPRs in the regulation of inflammatory responses as a complement to other excellent reviews of more facets of FPRs [2], [3], [19], [39], [40].
FPRs guide leukocyte trafficking in pathophysiological conditions
FPRs promote the differentiation and proliferation of immune cells
FPRs participate in the control tumor-associated inflammation and immune responses Chronic inflammation is an aberrantly prolonged form of a protective host response to the loss of tissue homeostasis [93], which has been recognized also a causative factor of many cancer. In fact, inflammation and neoplasia co-develop into “wounds that do not heal” [93]. Leukocytes, such as neutrophils, monocytes, macrophages, and eosinophils, provide soluble factors including metabolites of arachidonic acid, cytokines, chemokines, and free radicals, that may benefit the development of inflammation-associated cancer [94]. A wide array of chronic inflammatory conditions predispose susceptible cells to neoplastic transformation, Most of which are of epithelial cell origin (carcinomas) such as colon cancer linked to inflammatory bowel disease (IBD, chronic ulcerative colitis and Crohn's disease), esophageal adenocarcinoma associated with reflux esophagitis (Barrett's esophagus), hepatitis predisposing to cirrhosis and subsequent liver cancer, schistosomiasis associated with bladder and colon cancer, and Helicobacter infection leading to cancer of the stomach [93], [94]. The contribution of FPRs to inflammation-associated cancer has been increasingly recognized, which is illustrated in following chapters.
Detrimental effects of FPRs hijacked by tumor cells
Conflict of interest
Authors' note
Acknowledgement
2. This project was funded in part by federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E and was supported in part by the Intramural Research Program of the NCI, NIH.
Introduction Systemic inflammatory response syndrome (SIRS) is a serious condition associated with multiple organ dysfunction and failure. In 1992, the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference concluded that the diagnosis of SIRS requires the same criteria as sepsis, minus the presence of infection [1]. Therefore, the diagnostic criteria for SIRS include the presence of two or more of the following: hypothermia or hyperthermia, tachycardia, tachypnea, and abnormal white blood cell count. If unresolved, SIRS may lead to hypotension, vascular leakage, disseminated coagulation, organ failure and death [1]. SIRS can be seen following a variety of insults, such as trauma, burns or acute myocardial infarction.