Burkitt lymphoma expresses oncofetal chondroitin sulfate without being a reservoir for placental malaria sequestration
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Burkitt lymphoma expresses oncofetal chondroitin sulfate without being a reservoir for placental malaria sequestration. / Agerbaek, Mette Ø; Bento Ayres Pereira, Marina Maria; Clausen, Thomas M; Pehrson, Caroline; Oo, Htoo Zarni; Spliid, Charlotte; Rich, Jamie R; Fung, Vincent; Nkrumah, Francis; Neequaye, Janet; Biggar, Robert J; Reynolds, Steven J; Tosato, Giovanna; Pullarkat, Sheeja T; Ayers, Leona W; Theander, Thor G; Daugaard, Mads; Bhatia, Kishor; Nielsen, Morten A; Mbulaiteye, Sam M; Salanti, Ali.
In: International Journal of Cancer, Vol. 140, No. 7, 2017, p. 1597–1608.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Burkitt lymphoma expresses oncofetal chondroitin sulfate without being a reservoir for placental malaria sequestration
AU - Agerbaek, Mette Ø
AU - Bento Ayres Pereira, Marina Maria
AU - Clausen, Thomas M
AU - Pehrson, Caroline
AU - Oo, Htoo Zarni
AU - Spliid, Charlotte
AU - Rich, Jamie R
AU - Fung, Vincent
AU - Nkrumah, Francis
AU - Neequaye, Janet
AU - Biggar, Robert J
AU - Reynolds, Steven J
AU - Tosato, Giovanna
AU - Pullarkat, Sheeja T
AU - Ayers, Leona W
AU - Theander, Thor G
AU - Daugaard, Mads
AU - Bhatia, Kishor
AU - Nielsen, Morten A
AU - Mbulaiteye, Sam M
AU - Salanti, Ali
N1 - © 2016 UICC.
PY - 2017
Y1 - 2017
N2 - Burkitt lymphoma (BL) is a malignant disease, which is frequently found in areas with holoendemic Plasmodium falciparum malaria. We have previously found that the VAR2CSA protein is present on malaria-infected erythrocytes and facilitates a highly specific binding to the placenta. ofCS is absent in other non-malignant tissues and thus VAR2CSA generally facilitates parasite sequestration and accumulation in pregnant women. In this study, we show that the specific receptor for VAR2CSA, the oncofetal chondroitin sulfate (ofCS), is likewise present in BL tissue and cell lines. We therefore explored whether ofCS in BL could act as anchor site for VAR2CSA-expressing infected erythrocytes. In contrast to the placenta, we found no evidence of in vivo sequestering of infected erythrocytes in the BL tissue. Furthermore, we found VAR2CSA-specific antibody titers in children with endemic BL to be lower than in control children from the same malaria endemic region. The abundant presence of ofCS in BL tissue and the absence of ofCS in non-malignant tissue encouraged us to examine whether recombinant VAR2CSA could be used to target BL. We confirmed the binding of VAR2CSA to BL-derived cells and showed that a VAR2CSA drug conjugate efficiently killed the BL-derived cell lines in vitro. These results identify ofCS as a novel therapeutic BL target and highlight how VAR2CSA could be used as a tool for the discovery of novel approaches for directing BL therapy.
AB - Burkitt lymphoma (BL) is a malignant disease, which is frequently found in areas with holoendemic Plasmodium falciparum malaria. We have previously found that the VAR2CSA protein is present on malaria-infected erythrocytes and facilitates a highly specific binding to the placenta. ofCS is absent in other non-malignant tissues and thus VAR2CSA generally facilitates parasite sequestration and accumulation in pregnant women. In this study, we show that the specific receptor for VAR2CSA, the oncofetal chondroitin sulfate (ofCS), is likewise present in BL tissue and cell lines. We therefore explored whether ofCS in BL could act as anchor site for VAR2CSA-expressing infected erythrocytes. In contrast to the placenta, we found no evidence of in vivo sequestering of infected erythrocytes in the BL tissue. Furthermore, we found VAR2CSA-specific antibody titers in children with endemic BL to be lower than in control children from the same malaria endemic region. The abundant presence of ofCS in BL tissue and the absence of ofCS in non-malignant tissue encouraged us to examine whether recombinant VAR2CSA could be used to target BL. We confirmed the binding of VAR2CSA to BL-derived cells and showed that a VAR2CSA drug conjugate efficiently killed the BL-derived cell lines in vitro. These results identify ofCS as a novel therapeutic BL target and highlight how VAR2CSA could be used as a tool for the discovery of novel approaches for directing BL therapy.
U2 - 10.1002/ijc.30575
DO - 10.1002/ijc.30575
M3 - Journal article
C2 - 27997697
VL - 140
SP - 1597
EP - 1608
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 7
ER -
ID: 173238339