If you are like me and are kept up at night wondering about the relationship between placental cells and cancer cells, then get ready to start sleeping again. Researchers at the University of British Columbia were investigating these seemingly unrelated cell types when they uncovered a potential method to target and kill cancer cells. If that isn’t odd enough, the researchers killed the cancer cells using the parasite which causes malaria.
Infants, children and pregnant women are more vulnerable to malarial infections. Of all parasitic infections, malaria is the most common infection of pregnant women in the world, causing about 50 million cases per year (Brabin et al., 2004). The key feature of placental malaria pathogenesis is the binding of infected blood cells to other healthy cells in the placenta. By attaching to healthy cells, the parasite avoids being cleared out from the host by the immune system.
Once the malaria parasite Plasmodium falciparum, infects blood cells of the host, the parasite produces proteins that coat the surface of the blood cell, allowing it to bind and interact with specific cell types. One of these proteins, called VAR2CSA, is responsible for binding to placental cells. VAR2CSA binds to a specific type of sugar called chondroitin sulfate (CS). Although many cells contain CS, blood cells infected with malaria only bind onto placental CS (pl-CS) suggesting placental cells contain a unique type of CS. The pl-CS is associated with the ability of placental cells to invade the uterine tissue promoting rapid cell proliferation as part of normal placental growth. Proliferation and invasion are also observed in tumor cells, which led the researchers to hypothesize that both placental and cancer cells may contain similar CS. Furthermore the researchers investigated if there was an interaction between VAR2CSA and pl-CS in cancer cells.
Why is this important? If cancer cells contain pl-CS then the malaria protein VAR2CSA could be used to target those cancer cells in a similar manner to which it interacts with placental cells. As predicted, they found that epithelial, breast, bone and soft tissue cancer cells contain higher levels of pl-CS when compared to normal tissue. As well, they found that cancer cells containing higher levels of pl-CS could be used to predict disease progression and outcome in melanoma and lung cancer. For example, patients whose tumors expressed higher levels of pl-CS were predictive of more advanced stages of melanoma.
The researchers engineered a protein similar to the malarial VAR2CSA and called it rVAR2.The researchers developed two different rVAR2 proteins, one conjugated to a toxin and one conjugated to an anti-cancer drug. To test these two conjugated proteins, they used a mouse model in which a prostate cancer tumor from a patient was implanted directly into an immunodeficient mouse. After treatment with rVAR2 conjugated to the toxin or drug, tumor growth was inhibited, while the healthy tissue of the mice was unaffected.
The extraordinary work conducted by a group of researchers at the University of British Columbia has shown that they can exploit a protein produced by the malaria parasite for the treatment of cancer. By targeting the pl-CS chains present on cancer cells, this group has shown a potential new strategy of targeting cancer cells by using rVAR2 to deliver anti-cancer drugs specifically to the tumor environment. As well, rVAR2 binding to cancer cells could also be utilized as a marker for cancer progression and outcome for select tumors in patients.
Brabin, B. J., Romagosa, C., Abdelgalil, S., Menéndez, C., Verhoeff, F. H., McGread, R., Fletcher, K.A., Owens, S., d'Alessandro, U., Nosten, F., Fischer, P.R., and Ordi, J. (2004). The sick placenta-the role of malaria. Placenta, 25(5), 359–378. doi:10.1016/j.placenta.2003.10.019
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