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A novel IgM-H-ficolin complement pathway to attack allogenic cancer cells in vitro.

Lei X, Liu C, Azadzoi K, Li C, Lu F, Xiang A, Sun J, Guo Y, Zhao Q, Yan Z, Yang J - Sci Rep (2015)

Bottom Line: Ficolins, a group of oligomeric lectins with an overall structure similar to C1q and mannose-binding lectin (MBL) participate in microbe infection and apoptotic cell clearance by activating the complement lectin pathway or a primitive opsonophagocytosis.Here we report a natural cancer killing of different types of cancer cells by sera from a healthy human population mediated by a novel IgM-H-ficolin complement activation pathway.Our data suggest that the IgM-H-ficolin -mediated complement activation pathway may be another defensive strategy for human cancer immunosurveillance.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, School of Pharmacy, the Fourth Military Medical University, Xi'an, 710032 China.

ABSTRACT
The pentameric serum IgMs are critical to immune defense and surveillance through cytotoxicity against microbes and nascent cancer cells. Ficolins, a group of oligomeric lectins with an overall structure similar to C1q and mannose-binding lectin (MBL) participate in microbe infection and apoptotic cell clearance by activating the complement lectin pathway or a primitive opsonophagocytosis. It remains unknown whether serum IgMs interplay with ficolins in cancer immunosurveillance. Here we report a natural cancer killing of different types of cancer cells by sera from a healthy human population mediated by a novel IgM-H-ficolin complement activation pathway. We demonstrate for the first time that H-ficolin bound to a subset of IgMs in positive human sera and IgM-H-ficolin deposited on cancer cells to activate complement attack in cancer cells. Our data suggest that the IgM-H-ficolin -mediated complement activation pathway may be another defensive strategy for human cancer immunosurveillance.

No MeSH data available.


Related in: MedlinePlus

Anti-tumor activity in healthy human sera.(a) Representative images of typical cytolysis in KATO III cells were taken by optical microscopy and (b) transmission electron microscopy. PHS: positive human serum with a cytolysis percentage >20%. (c) The cancer cell KATO III destruction activity of compatible sera.
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f1: Anti-tumor activity in healthy human sera.(a) Representative images of typical cytolysis in KATO III cells were taken by optical microscopy and (b) transmission electron microscopy. PHS: positive human serum with a cytolysis percentage >20%. (c) The cancer cell KATO III destruction activity of compatible sera.

Mentions: Because cancer-specific IgMs were reported to pre-exist in humans1516, we proposed that human sera from healthy populations should kill different cancer cells without involvement of cellular components. Human sera samples were collected from 1000 healthy donors (Table 1) and stomach cancer KATO III cells were first incubated with the sera. Because aberrant expression of ABO antigens is frequently observed in a variety of cancer cells1718, and anti-A and anti-B antibodies of human sera are usually IgM type, cytolysis may occur when blood isoantigen to cancer cells meets its corresponding isoantibody in vitro, similar to a specific hemolysic reaction. Because KATO III cells express B antigen, to exclude the cytolysis triggered by incompatibility of anti-B isoantibody and B isoantigen, we examined and confirmed the cytolysis of KATO III cells in matched sera (including sera collected from humans whose blood type was AB and B) by microscopy and electron microscopy (Fig. 1a and 1b). Serum causing greater than 20% cell death was set as positive human serum (PHS) for KATO III cells, and that causing 20% or less was designated negative human serum (NHS). Sera from 35.4% of compatible healthy individuals were found to be positive for killing KATO III cancer cells (Fig. 1c and Table 2).


A novel IgM-H-ficolin complement pathway to attack allogenic cancer cells in vitro.

Lei X, Liu C, Azadzoi K, Li C, Lu F, Xiang A, Sun J, Guo Y, Zhao Q, Yan Z, Yang J - Sci Rep (2015)

Anti-tumor activity in healthy human sera.(a) Representative images of typical cytolysis in KATO III cells were taken by optical microscopy and (b) transmission electron microscopy. PHS: positive human serum with a cytolysis percentage >20%. (c) The cancer cell KATO III destruction activity of compatible sera.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4296296&req=5

f1: Anti-tumor activity in healthy human sera.(a) Representative images of typical cytolysis in KATO III cells were taken by optical microscopy and (b) transmission electron microscopy. PHS: positive human serum with a cytolysis percentage >20%. (c) The cancer cell KATO III destruction activity of compatible sera.
Mentions: Because cancer-specific IgMs were reported to pre-exist in humans1516, we proposed that human sera from healthy populations should kill different cancer cells without involvement of cellular components. Human sera samples were collected from 1000 healthy donors (Table 1) and stomach cancer KATO III cells were first incubated with the sera. Because aberrant expression of ABO antigens is frequently observed in a variety of cancer cells1718, and anti-A and anti-B antibodies of human sera are usually IgM type, cytolysis may occur when blood isoantigen to cancer cells meets its corresponding isoantibody in vitro, similar to a specific hemolysic reaction. Because KATO III cells express B antigen, to exclude the cytolysis triggered by incompatibility of anti-B isoantibody and B isoantigen, we examined and confirmed the cytolysis of KATO III cells in matched sera (including sera collected from humans whose blood type was AB and B) by microscopy and electron microscopy (Fig. 1a and 1b). Serum causing greater than 20% cell death was set as positive human serum (PHS) for KATO III cells, and that causing 20% or less was designated negative human serum (NHS). Sera from 35.4% of compatible healthy individuals were found to be positive for killing KATO III cancer cells (Fig. 1c and Table 2).

Bottom Line: Ficolins, a group of oligomeric lectins with an overall structure similar to C1q and mannose-binding lectin (MBL) participate in microbe infection and apoptotic cell clearance by activating the complement lectin pathway or a primitive opsonophagocytosis.Here we report a natural cancer killing of different types of cancer cells by sera from a healthy human population mediated by a novel IgM-H-ficolin complement activation pathway.Our data suggest that the IgM-H-ficolin -mediated complement activation pathway may be another defensive strategy for human cancer immunosurveillance.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, School of Pharmacy, the Fourth Military Medical University, Xi'an, 710032 China.

ABSTRACT
The pentameric serum IgMs are critical to immune defense and surveillance through cytotoxicity against microbes and nascent cancer cells. Ficolins, a group of oligomeric lectins with an overall structure similar to C1q and mannose-binding lectin (MBL) participate in microbe infection and apoptotic cell clearance by activating the complement lectin pathway or a primitive opsonophagocytosis. It remains unknown whether serum IgMs interplay with ficolins in cancer immunosurveillance. Here we report a natural cancer killing of different types of cancer cells by sera from a healthy human population mediated by a novel IgM-H-ficolin complement activation pathway. We demonstrate for the first time that H-ficolin bound to a subset of IgMs in positive human sera and IgM-H-ficolin deposited on cancer cells to activate complement attack in cancer cells. Our data suggest that the IgM-H-ficolin -mediated complement activation pathway may be another defensive strategy for human cancer immunosurveillance.

No MeSH data available.


Related in: MedlinePlus