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Characterization of gene-modified breast cancer cells for MARS imaging

A 2019/2020 Summer Studentship research project

Clinically, HER2 status is assessed once via collection of tissue biopsies with laboratory analysis and subsequently considered homogenous across a tumour and constant during the progression of breast cancer. This suggests that anti-HER2 therapy would successfully target all of the tumour cells in patients with HER2-postive breast cancer. However, variations across tumours and over time of cancer progression or therapy have been reported, resulting in treatment failure in some patients. Our research aims to detect HER2 in patient’s tumours non-invasively using MARS spectral CT. Insights derived from this information would enable the clinician to change the treatment accordingly.

Student: Jaya Montecillo
Supervisors: Dr Aamir Raja and Associate Professor Gabi Dachs
Sponsor: Breast Cancer Foundation NZ

Introduction

Treatment for breast cancer varies depending on the specific features of the tumour. Trastuzumab (Herceptin) is an antibody that specifically targets tumours expressing the human epidermal growth factor receptor 2 (HER2). Trastuzumab is an effective clinical treatment for cancer patients that have HER2 positive tumours, but ineffective against HER2 negative tumours. HER2 expression can vary across a tumour and reduce over time, thus making trastuzumab treatment less effective. Thus, treatment failure can be due to unrecognized changes and variations in HER2 expression. A new form of imaging, MARS spectral CT, offers an opportunity to detect these variations non-invasively. We have demonstrated that human cells expressing HER2 can be visualized by MARS using gold-labelled trastuzumab. Prior to testing the feasibility of this approach in patients with cancer, we need to produce a preclinical (murine) model that expresses the human HER2 protein. Normally, mouse tumours would not express HER2, and would therefore not be suitable. We have therefore gene-modified murine breast cancer cells to express human HER2. The goal of this project is to further characterize these cells with the ultimate aim of imaging tumour-bearing mice by MARS.

Aim

The aim of this study is to characterize murine breast cancer cells that have been gene-modified to express human HER2 in vitro and, potentially, in vivo.

Method

HER2-modified murine breast cancer cells will be characterized in vitro using a range of techniques, including cell proliferation analysis (cell counts, viability assays), Western blot analysis (antibodies targeted against human HER2, using human SKBr3 cells as positive controls), immunofluorescence (fluorescent-labelled anti-HER2 antibody), and MARS scanning of cell pellets (cells labelled with gold-conjugated trastuzumab alongside phantoms containing known quantities of gold-nanoparticles). Time-permitting, HER2-modified murine breast cancer cells will be implanted into C57/BL6 mice and characterized in vivo, including monitoring of tumour growth rate, detection of human HER2 ex vivo, and ultimately, by injection of gold-conjugated trastuzumab followed by MARS scanning.

Student researcher’s component of the study

The student will carry out all in vitro cell culture and associated assays, and analyze the data. Depending on how the cell culture assays progress, the student will get trained for the animal part of the project, and will then carry out the in vivo parts of the study with help from A/P Dachs. MARS scanning will be carried out by the MARS team.

Student Prerequisites

Science or health science student

How to apply

Email aamir.raja@otago.ac.nz