Author: stefania augeri
Date: 20/06/2013



BST1 gene is located on chromosomes 4p15 and encodes for a GPI anchored protein of 42-45 kDa. It is an ADP-ribosyl cyclase–related cell surface molecule and regulates leukocyte diapedesis during inflammation. BST1 is also involved in epithelial-mesenchimal transition of ovarian cancer and might be a good candidate as a therapeutic target for tumors characterized by high BST1 expression.



Protein Aminoacids Percentage


BST1 is an enzyme similar in function and structure to CD38. BST1 has a duplex activity: ADP-ribosyl ciclase and cADPR-hydrolase, the second prevails on the first. BST1 produces cADPR from NAD+, then it hydrolyzes cADPR obtaining ADPR. Its activity needs of particular conditions: a pH value between 4 and 6 and the presence of bivalent ions, such as Zn2+ and Mn2+. The ions Cu2+ inhibit BST1 activity. These facts suggest that the activity of BST1 is not rilevant in physiological condition. Its biological function is probably mediated by its interaction with integrins, in particular CD29 and CD18 (The CD157-integrin partnership controls transendothelial migration and adhesion of human monocytes, 2011).


Both CD38 and BST1 play dual roles as receptors and ectoenzymes. Its engagement regulates Ca2+ homeostasis and mediates superoxide (O2) production. BST1 plays a pivotal role in the control of leukocyte adhesion, migration and diapedesis.

Neutrophilis model
The importance of BST1 in the neutrophil diapedesis was demostrated using monoclonal antibodies: ligation of BST1 with monoclonal antibodies on the surface of neutrophilis results in altered neutrophil movement on the surface of endothelium and in loss of diapedesis. Studies revealed that this protein has a sort of compass during the interaction between endothelial cells and neutrophilis. The crosslinking of BST1 induce morfology modification in the cytoplasmic membrane of neutrophilis, including the formation of microprotrusion and lamellipodia. At the same time, BST1, that is fisiologically distributed all over the membrane, is concentrated in the uropod, in the opposite site of lamellipodia, that are regions rich of polimerized actin (CD157 is an important mediator of neutrophil adhesion and migration, 2004).

Following BST1 ligation, neutrophils appear disoriented, meandering toward junctions where they eventually stop without transmigrating (CD157 plays a pivotal role in neutrophil transendothelial migration 2006).

Monocytes model
BST1 is prevalently located within the detergent-resistant membrane microdomains (lipid raft) to which, upon clustering, it promotes the recruitment of CD18 and CD29 integrin, which, in turn, leads to the formation of a multimolecular complex favoring signal transduction. This functional cross-talk with integrins allows BST1 to act as a receptor despite its intrinsic structural inability to do so on its own. Intracellular signals mediated by BST1 rely on the integrin/Src/FAK (focal adhesion kinase) pathway, resulting in increased activity of the MAPK/ERK1/2 and the PI3K/Akt downstream signaling pathways, which are crucial in the control of monocyte transendothelial migration. Collectively, these findings indicate that BST1 acts as a molecular organizer of signaling-competent membrane microdomains and that it forms part of a larger molecular machine ruled by integrins. The CD157-integrin partnership provides optimal adhesion and transmigration of human monocytes (The CD157-integrin partnership controls transendothelial migration and adhesion of human monocytes, 2011).

Ovarian cancer model
The involvement of BST1 in the control of leukocyte trafficking and its expression outside the myeloid compartment primarily in mesothelial cells, led to hypothesize that BST1 could be expressed by epithelial ovarian cancer cells and could be involved in the control of tumor dissemination. BST1 is involved in EMT of ovarian cancer cells. Indeed, exogenous expression of BST1 promotes morphological, phenotypic and functional changes that are considered the hallmarks of mesenchymal differentiation. The expression of BST1 led to the expression of molecules that are reported to identify a subset of cells with a stem-like phenotype, such as EpCAM, CD24 and SSEA4 (Stage-specific embryonic antigen 4). The connection between EMT and cancer stem cell generation has a detrimental effect on cancer progression because it entails the acquisition of cellular traits associated with high-grade malignancy and with self-renewal ability, both of which foster metastatic dissemination. BST1-positive cells show accelerated growth and a higher proliferation rate than the negative counterpart, resulting in a significantly greater tumorigenic potential in vivo (Biological Role, Clinical Significance and Potential Therapeutic Applications of CD157 in Ovarian Cancer, 2013, in press).

Tissue distribution (CD38 and CD157: A long journey from activation markers to multifunctional molecules, 2013)


Augeri Stefania
Mariani Valentina

2013-06-20T17:22:47 - stefania augeri
2013-06-20T15:42:07 - stefania augeri
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