Co-culture of Ovarian Cancer and Stromal Cells Using a Novel 3-D Model

Overview

Topic status: We're looking for students to study this topic.

Ovarian cancer is the leading cause of gynecological cancer deaths in Australian women. Around 1,200 women are diagnosed with ovarian cancer each year in Australia of which two-thirds are at an advanced disease stage leading to a poor prognosis. Although most patients respond initially to surgery and chemotherapy, resistance occurs and only 4 out of 10 women survive for 5 years beyond their diagnosis. Ovarian cancer cells can then spread into the peritoneal cavity, form multicellular aggregates to survive and subsequently attach to the stromal cell layer, invade into the underlying extracellular matrix and grow secondary tumors, which is clearly the critical step leading to the poor outcome. However, events mediating the communication between cancer cells and the surrounding matrix that are involved in patient responses to chemotherapy are unknown. Therefore, novel three-dimensional cell culture models have been employed to explore cell-cell and cell-matrix interactions and chemoresistance in physiological microenvironments representative of that seen in patients.

Hypothesis: Kallikrein proteases, in particular kallikrein 7, promote multicellular
aggregation via the integrin, signalling pathway, in particular "5"1, and chemoresistance to clinically administered anti-cancer drugs, such as paclitaxel, in human ovarian cancer.

Aim 1. To establish co-cultures of ovarian cancer and stromal cells within 3-D matrices

Aim 2. To study the responsiveness of co-cultures towards anti-cancer drugs

Methods and techniques that will be developed in the course of this project:

  • Cell culture to grow cancer and stromal cells within a 3-D platform3
  • Confocal microscopy to image co-cultures and formation of multicellular aggregates
  • Western Blot analyses to measure protein expression upon co-culture
  • Polymerase chain reactions (PCR) to detect gene expression upon co-culture
  • Chemosensitivity assays to quantify chemotreatment of co-cultures
Study level
PhD, Honours
Supervisors
QUT
Organisational unit

Science and Engineering Faculty

Research area

Cell and Molecular Biosciences

Contact

Please contact the supervisor.