Natural antimicrobial peptides are present in different compartments (eggshell, egg white, and vitelline membranes) of the hen egg and are expected to be involved in the protection of the embryo during its development and to contribute to the production of pathogen-free eggs. In the present study, we used vitelline membranes from hen (Gallus gallus) eggs as a source of avian -defensin 11 (AvBD11). A purification scheme using affinity chromatography and reverse-phase chromatography was developed. Purified AvBD11 was analyzed by a combination of mass spectrometry approaches to characterize its primary sequence and structure. A monoisotopic molecular species at [M ؉ H]؉ of 9,271.56 Da was obtained, and its N-and C-terminal sequences were determined. We also examined posttranslational modifications and identified the presence of 6 internal disulfide bonds. AvBD11 was found to exhibit antimicrobial activity toward both Gram-positive and Gram-negative bacteria.The avian egg is a unique and original biological system which is formed according to a well-defined spatial and temporal sequence as it passes along the reproductive tract of the hen. The segments of the oviduct involved in the egg formation are the infundibulum, the magnum, the isthmus, and the uterus. Each segment expresses and secretes specific molecules that become successively incorporated into the vitelline membranes in the infundibulum, the egg white in the magnum, the eggshell membranes in the isthmus, and the eggshell in the uterus. Thus, the hen deposits into the egg, which can be considered a closed chamber, all the nutrients and protective systems that are necessary to support the development of an embryo during 21 days of incubation. Recently, transcriptomic and proteomic approaches have identified almost 1,000 putative proteins and peptides in the various compartments of eggs (6). Among these are a number of polypeptides that are likely to resist microbial contamination of the eggs, some of which belong to the family of avian -defensins (AvBDs).A total of 14 avian -defensin genes have been identified through in silico studies. Because most of them were simultaneously described by two research groups, some confusion was generated due to different nomenclatures (9,10,18,31). In a collaborative venture, we proposed a novel nomenclature that adopted the numbering system used by Xiao et al. (31) and replaced the term "gallinacin," used formerly by Lehrer's group, with "avian -defensin" (AvBD) (19). AvBDs are small cationic nonglycosylated peptides (1 to 9 kDa). Some of them were successfully tested for their antimicrobial activity, including chicken AvBDs AvBD1, -2, -7, and -9, turkey AvBD1 and -2, ostrich AvBDs AvBD1, -2, -7, and -8, and penguin AvBD103b (3, 30). In mammals, -defensins are molecules of innate and adaptive immunity, with a broad spectrum of antimicrobial activity (1). -Defensin molecules possess six highly conserved cysteines with the following consensus sequence motif, where C is a cysteine, G a glycine, and X any amino acid: X...
Platelets are small anucleated cell fragments that ensure the arrest of bleeding after a vessel wall injury. They are also involved in non-hemostatic function such as development, immunity, inflammation, and in the hematogeneous phase of metastasis. While the role of platelets in tumor metastasis has been recognized for 60 years, the molecular mechanism underlying this process remains largely unclear. Platelets physically and functionally interact with various tumor cells through surface receptors including integrins. Platelets express five integrins at their surface, namely α2β1, α5β1, α6β1, αvβ3, and αIIbβ3, which bind preferentially to collagen, fibronectin, laminin, vitronectin, and fibrinogen, respectively. The main role of platelet integrins is to ensure platelet adhesion and aggregation at sites of vascular injury. Two of these, α6β1 and αIIbβ3, were proposed to participate in platelet–tumor cell interaction and in tumor metastasis. It has also been reported that pharmacological agents targeting both integrins efficiently reduce experimental metastasis, suggesting that platelet integrins may represent new anti-metastatic targets. This review focuses on the role of platelet integrins in tumor metastasis and discusses whether these receptors may represent new potential targets for novel anti-metastatic approaches.
Our data uncovers a novel paracrine interaction between tumor pericytes and inflammatory cells and delineates the cellular events resulting in the recruitment of MDSC to tumors. Furthermore, we propose for the first time a role for tumor pericytes in modulating the expression of immune mediators in malignant cells by promoting a hypoxic microenvironment.
Tissue factor pathway inhibitor-2 (TFPI-2) is a potent inhibitor of plasmin, a protease which is involved in tumour progression by activating (MMPs). This therefore makes TFPI-2 a potential inhibitor of invasiveness and the development of metastases. In this study, low levels of TFPI-2 expression were found in 65% of patients with small cell lung cancer (SCLC), the most aggressive type of lung cancer. To study the impact of TFPI-2 in tumour progression, TFPI-2 was overexpressed in NCI-H209 SCLC cells which were orthotopically implanted in nude mice. Investigations showed that TFPI-2 inhibited lung tumour growth. Such inhibition could be explained in vitro by a decrease in tumour cell viability, blockade of G1/S phase cell cycle transition and an increase in apoptosis shown in NCI-H209 cells expressing TFPI-2. We also demonstrated that TFPI-2 upregulation in NCI-H209 cells decreased MMP expression, particularly by downregulating MMP-1 and MMP-3. Moreover, TFPI-2 inhibited phosphorylation of the MAPK signalling pathway proteins involved in the induction of MMP transcripts, among which MMP-1 was predominant in SCLC tissues and was inversely expressed with TFPI-2 in 35% of cases. These results suggest that downregulation of TFPI-2 expression could favour the development of SCLC.
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