Overview
Topic status: We're looking for students to study this topic.
Epithelial ovarian cancer (EOC) is the leading cause of death in gynaecological tumours. 75% of patients are diagnosed after tumours have spread to the abdominal cavity (metastasis). 50% present to doctors with an accumulation of fluid in their abdominal cavities (ascites). In this scenario, patients not only have cancers embedded in solid stroma in primary and metastatic sites but also cancer cells floating in ascites. The treatment for ovarian cancer has been surgery followed by cytotoxic chemotherapy. Unfortunately, most patients develop resistance to the treatment leading to a 5-year overall survival rate at 30%. Thus, we need to better understand the behaviours of EOC cells in these environments to develop more efficient therapeutic strategies.
The expression of several Kallikrein (KLKs) is related to short survival time in ovarian cancer patients and KLK4, KLK5 and KLK7 are highly expressed in serous EOC. KLK4 and KLK7 aid cancer cells survival in 3-dimensional (3D) suspension, an ascites mimicry in the patients, by inducing cancer cells to aggregate which is related to chemoresistance. In 3D-suspension, KLK4-transfected SKOV3 cells showed consistent Src-activation and increased lipocalin 2; two known chemoresistance relevant proteins. We also found a different expression pattern of cell survival signals between monolayer and suspension cultured ovarian cancer cells. To better understand the roles of KLKs, factors and their relevant cell signalling networks involved in ovarian cancer environments, we will determine the expression of these signals in serous EOC cells cultured in 2D-monolayer, 3D-suspension and 3D-solid matrices.
Hypothesis: KLK proteases and their relevant factors make cancer cells more invasive and more resistant to anti-cancer treatment, and involve multi-cellular signalling networks in different tumour microenvironments
- Aim 1: To culture ovarian cancer cells with/without KLKs in 3D-suspension and 3Dmatrices
- Aim 2: To determine the relevant cell signalling networks involved in these environments
- Aim 3: To determine the cell proliferation, adhesion, migration and invasion genes
- Aim 4: To determine cell response to chemotherapy +/- inhibitors to KLK & relevant proteins
Methods and techniques that will be developed in the course of this project:
- Cell cultures include 2-dimensional (2D) monolayer, 3D-suspension and 3D-matrices and chemosensitivity assays
- RT-PCR, microarray, protein array, Western blot analysis, immunohistochemistry and immunofluorescent microscopy
- Study level
- PhD, Honours
- Supervisors
- QUT
- Organisational unit
Science and Engineering Faculty
- Research area
- Contact
- Please contact the supervisor.
Dr Ying Dong
Professor Judith Clements
