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Studying a 3D model of breast cancer to investigate protein changes driven by a fat-rich environment

A 2020/2021 Summer Studentship research project

Student: Maddison Hill
Supervisors: Dr Elisabeth Phillips, Associate Professor Margaret Currie
Sponsor: Cancer Society, Canterbury-West Coast Division

Introduction

Breast cancer exists in an extremely lipid rich environment. Our laboratory seeks to explore the interaction between breast cancer cells and the stromal fat cells. In order to do this, we have used 2D trans-well co-cultures; whereby, human breast cancer cell lines are grown together with human breast adipocytes (fat cells). Growing the cells in co-culture exposes the breast cancer cells to numerous inflammatory cytokines produced by the adipocytes cells at a local level, and has a remarkable impact on both the adipocytes and cancer cells. In vitro, we have shown the cancer cells become more resistant to chemotherapy and more motile, and the adipocytes become de-differentiated, and secrete factors that promote the survival and migration of the breast cancer cells.

We have measured the global protein changes in both the cancer cells and the in the proteins secreted by the fat cells in this 2D system using discovery mass spectrometry, and aim to measure these changes in our novel 3D hydrogel co-culture model developed in-house.

Aim

This research is important because it will increase our understanding of the breast cancer local microenvironment, where cancer cells develop and grow in fat rich tissue. It will bring together our intriguing data collected from the 2D co-culture system and investigate these in the more biologically relevant, recently characterised 3D co-culture system. This work will form part of a manuscript and pilot data for future grant proposals. Together with research ongoing in MCRG may lead to identification and characterisation of biomarkers of fat driven cancer progression, and to development of chemotherapeutics to target the fat-rich tumour microenviroment in breast cancer patients.

Method

The student will perform immunofluorescence (IF) and/or immunohistochemistry (IHC) on samples from our 3D co-culture model. We have discovered multiple protein changes through our 2D co-culture studies, the summer studentship will initially focus on two candidate proteins; 1) a protein secreted by adipocytes, and is heavily associated with promotion of metastasis and invasion in other cancers, and 2) a protein that showed higher abundance in cancer cells grown with adipocytes and is associated with chemotherapy resistance.

The proposed summer-studentship represents an important part of our ongoing research into the role of adipocytes in the progression of cancer, and designed for completion within a 10 week Summer-Studentship.

Student researcher’s component of the study

The student will prepare the sections, perform all laboratory experiments (IF, IHC) and evaluate the results under the laboratory supervision of experienced scientific researchers in the Mackenzie Cancer Research Group.

Student prerequisites

We are looking for a bright, enthusiastic student with good laboratory experience.