Role of WNT signalling in the regulation of COX-2 expression in breast cancer

Abstract

Breast cancer is one of the most common cancers in the world, and has therefore been widely researched the last decades. Breast cancer is one of the least aggressive cancer types, and this together with extensive research has given one of the highest survival rate of any cancer types. However, there is still a long way to go in order to decrease the number of deaths even further. New, more effective treatments with less adverse effect than the commonly used chemo- and radiation therapies are in high demand, especially in order to treat more aggressive types of breast cancers such as triple negative breast cancer. Roughly 15% of breast cancers consists of triple negative breast cancer cells, these are highly invasive cells prone to metastasis and lack the ER, PR and HER2 receptors commonly targeted in traditional breast cancer therapies. This means that new therapies are of great necessity in these cancer types. A potential target that has been suggested in studies is the WNT ligand WNT5A. Loss of WNT5A expression in breast cancer has been shown to be a poor prognostic marker indicated in increased invasion and thus metastasis of the cancer cells. In this study, we aimed to examine the potential use of WNT5A as a COX-2 regulator. Increased COX-2 expression in breast cancer tumours is highly associated with a bad prognosis due to COX-2 regulated production of inflammatory prostaglandin PGE2. Increased COX-2 expression and thus increased PGE2 is associated with increased cancer cell invasion and metastasis as well as the inflammatory effects mentioned previously. In our study, we found that WNT5A can potentially cause a decrease in COX-2 protein expression in MDA-MB-231 and SUM159 breast cancer cells, and is thus potentially promising as a new treatment for triple negative breast cancer tumours.

Popular Abstract

WNT5A regulation of COX-2: a new way to battle breast cancer?

Cancer has become one of the most feared diseases in today’s society, claiming victims of all ages, genders, and nationalities. The battle against it is ongoing, with the need for new innovative treatments being stronger than ever. To win the war on cancer we need to have as many battle strategies as possible, and the key to this is through understanding the disease.

Breast cancer is one of the most common types of cancer, affecting millions of people each year. Many treatments used today are chemo-and radiation therapies, that are very difficult for the patients to go through. We therefore desperately need to find more effective ways to conquer breast cancer. The environment in the body is very different in an individual with cancer as opposed to a healthy individual, as the cancer attempts to control the environment and to enable the cancer cells to grow and spread, usually causing inflammation in the process. A protein that is well-known to be contributing to the body’s fight against breast cancer is WNT5A. It is known to be able to prevent the cancer cells from moving and forming tumours around the body, so-called metastasis, and expression of WNT5A is commonly lost in breast cancer. We wanted to see if WNT5A could be used to battle breast cancer on multiple frontiers by fighting both inflammation and metastasis. To do this, we examined if introducing WNT5A into the cancer cells that had lost the protein would decrease the expression of COX-2; a protein induced by cytokines that causes inflammation and metastasis in breast cancer.

In our experiments, we had three major strategies to prove that WNT5A could decrease COX-2 in breast cancer. First off, we created a high amount of COX-2 in the cells by stimulation with pro-inflammatory molecule IL-1β as this is how COX-2 production is stimulated in the body. Secondly, we treated the cells with WNT5A and studied the COX-2 expression to see if there was a decrease. Lastly, we also treated the cells with WNT3A, which is a protein that has opposite actions of WNT5A in breast cancer, to see if COX-2 expression increased with this treatment to allow us to get a fuller picture.

Our results showed that through introducing WNT5A in breast cancer cells, we were able to get a decrease in COX-2. As expected, we could also see an increase when cells were treated with WNT3A, further confirming that the WNT-proteins can regulate COX-2 expression. On the basis of this, WNT5A shows potential as a treatment for breast cancer patients as it is both capable of fighting metastasis on its own, and additionally also COX-2 regulated metastasis and inflammation. Through further studies and increased knowledge COX-2 regulation by WNT5A could be developed further, offering help in conquering breast cancer for patients in need.






Master’s Degree Project in Molecular Biology 45 credits 2019
Department of Biology, Lund University

Supervisors: Tommy Andersson and Mansi Manchanda
Division of Cell and Experimental Pathology, Department of Translational Medicine, Lund University,
Clinical Research Centre, Skåne University Hospital, SE-20213 Malmö, Sweden

• author: Engström, Linn
• supervisor: Mansi Manchanda; Tommy Andersson
• organization: Degree Projects in Molecular Biology
• course: MOBN02 20182
• year: 2019
• type: H2 - Master's Degree (Two Years)
• subject: Biology and Life Sciences
• language: English
• id: 8979274
• date added to LUP: 2019-06-04 11:47:49
• date last changed: 2019-06-04 11:47:49