Understanding the role of tumour microenvironments on ovarian cancer phenotypes

Overview

Topic status: In progress

Overview

Most of ovarian cancer patients are diagnosed when tumours have spread in the abdominal cavity growing many cancerous nodules (metastasis). More than half of them present to doctors with an accumulation of fluid in their abdominal cavities (ascites). In this scenario, patients have not only the cancers grown in solid stroma in primary and metastatic sites but also tumour cells floating in ascites fluid after shedding from these sites. The current treatment including surgery and chemotherapy has remained ~30% 5-year overall survival for late stage patients. Thus, a better understanding of the different phenotypes/behaviours of ovarian cancer cells in ascites fluid suspension versus solid stroma is needed for efficacious treatment.

To mimic ascites in ovarian cancer patients, we established a 3-dimensional (3D)-suspension cell culture model in which kallikrein (KLK)7 helps cancer cells stick together (aggregation). Multicellular aggregation (MCA) aids cancer cells invasion into the abdominal membrane and is related to chemoresistance. We also observed a dynamic alteration of epithelial phenotypes which has been found in ovarian cancer progression. Recent studies have revealed that microRNA200 family members and transcriptional factor ZEB1 and ZEB2 (SIP1) regulate ovarian cancer development and epithelial-mesenchymal phenotypes. However, it remains to clarify their association with the cell phenotypic plasticity and KLK7 enzyme in ovarian cancer progression such as, ascitic microenvironment and metastatic tumour cells. Thus, our hypotheses are that KLK7 and microRNA200 family members regulate the phenotypic plasticity in the tumour microenvironment and help ovarian cancer cells survive during the metastasis and resist to chemotherapy.

Research activities

We have collected RNA and protein from ovarian cancer cells with/without KLK7 cultured in 3D-suspension to mimic ascites and 3D-Matrigel to mimic solid tumour stroma in patients. We will determine the expression of KLK7, microRNA200 family members and E-cadherin using qRT-PCR and Western blot analysis.

Expected outcome: We will have generated data for the expression of KLK7, microRNA200s family members and related factors in ovarian cancer cells cultured in different models to mimic tumour microenvironments. These data will help better understand the phenotypic plasticity of ovarian cancer during the progression to improve the current treatment approaches.

Duration

  • 6 weeks
  • 1 to 21 December 2011 and 9 to 29 January 2012
  • 30 hours per week and 180 hours in total
Study level
Vacation research experience scholarship
Supervisors
QUT
Organisational unit

Science and Engineering Faculty

Research area

Cell and Molecular Biosciences

Keywords
microenvironments, tumour microenvironments, tumour, ovarian cancer, ovarian cancer phenotypes, cancer phenotypes, cancer, VRES
Contact

For more information please contact Dr Ying Dong or Prof Judith Clements.