Loading...

Thursday July 27 2017

Targeting Cancers with a Malarial Protein

What type of cells multiplies rapidly, invades surrounding tissue, and even takes over the arrangement of blood vessels nearby? If you said, “Cancer cells,” think again. That is not to say that you are wrong. In fact, quite the opposite is true. Enhanced proliferation, along with invasion and implantation in neighbouring tissue, is a hallmark of cancer. However, I tell you to think again because these are, in fact, activities that cells in the placenta share with cancer cells.1,2  

Because of this, researchers, including Dr. Ali Salanti from the University of Copenhagen and his team, have been interested in identifying traits that are similar in the growth of both the placenta and a tumour.2 Dr. Salanti and his team described, in a paper published just last month, a specific type of modified carbohydrate chain that is present on the surface of both placental cells and tumour cells and is exclusively targeted by a malarial protein.1

It was noticed a long time ago that malaria affects pregnant women more severely; pregnant women are 3 times more likely to experience severe forms of the disease than other women, likely because of the decrease in immunity that is commonly seen in pregnancy and the collection of infected blood cells in the placenta.3 The most deadly form of malaria is caused by an infection with a parasite known as Plasmodium falciparum, which is commonly transmitted by mosquito bites.3 The parasite eventually invades blood cells, triggering an immune response against these blood cells, particularly by the spleen.4 The malarial protein in question is a type of variant surface antigen (VAR2CSA) and is exposed on the surface of blood cells that have been infected with P. falciparum.4 The VAR2CSA protein anchors infected cells to specific sites in the placenta by interacting with a modified carbohydrate chain called CSA, which is found in the placenta.4 As the infected cells collect in the placenta, the risk of miscarriage, neonatal death, and also maternal death increases.3

Dr. Salanti’s team found that the CSA recognized by VAR2CSA is expressed only in the placenta.1 Previous research had shown that CSA has a role in proliferation and invasion by placental cells, so, as this is a trait shared with cancer cells, the team asked whether cancer cells might possess a similar modified carbohydrate chain.1 Analyzing samples from many forms of cancer, including brain tumours and leukemia, they found that CSA is actually present in more than 90% of human cancers.1,2 They also confirmed that VAR2CSA can target cancer cells in mouse models.1

Since VAR2CSA binds specifically to CSA, which is only found in the placenta and cancer cells in humans, this interaction presented itself as a method to target toxins specifically to tumours. By attaching a drug previously shown to inhibit tumour growth5 to VAR2CSA, the researchers were able to kill tumour cells and increase survival of treated mice.1 In some cases, just three doses was enough to cause the tumour to shrink.

A treatment such as this would be very specific and could be incredibly useful, particularly for dealing with skin cancers, which often spread throughout the body. The researchers hope to start human trials within four years.2

By Joella Ho

—-

References

  1.   Salanti A, Clausen TM, Agerbæk MØ, Al Nakouzi N, Dahlbäck M, Oo HZ, et al. Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein. Cancer Cell [Internet]. 2015 Oct [cited 2015 Oct 13];28(4):500–14. Available from: http://www.sciencedirect.com/science/article/pii/S1535610815003347
  2.   Malaria protein may hold key for cancer cure, scientists say. Fox News [Internet]. 2015 Oct 15 [cited 2015 Nov 12]. Available from: http://www.foxnews.com/health/2015/10/15/malaria-protein-may-hold-key-for-cancer-cure-scientists-say.html
  3.   Schantz-Dunn J, Nour NM. Malaria and Pregnancy: A Global Health Perspective. Rev Obstet Gynecol [Internet]. MedReviews, LLC; 2009;2(3):186–92. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2760896/
  4.   Takem EN, D’Alessandro U. Malaria in Pregnancy. Mediterr J Hematol Infect Dis [Internet]. Università Cattolica del Sacro Cuore; 2013 Jan 2;5(1):e2013010. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3552837/
  5.   F, Discafani CM, Annable T, Beyer C, Musto S, Hari M, et al. HTI-286, a Synthetic Analogue of the Tripeptide Hemiasterlin, Is a Potent Antimicrotubule Agent that Circumvents P-Glycoprotein-mediated Resistance in Vitro and in Vivo  . Cancer Res [Internet]. 2003 Apr 15;63 (8 ):1838–45. Available from: http://cancerres.aacrjournals.org/content/63/8/1838.abstract

RELATED POST

Leave a reply

The Meducator is McMaster University’s undergraduate Health Sciences Journal. It publishes pieces that critically address current issues with a high degree of scientific rigor, but in a way that is accessible to a broad audience.

NEWSLETTER

Enter your email address below to subscribe to my newsletter

CONNECT & FOLLOW
Meducator Spotlight
Recent Comments