Title
Investigating epithelial–mesenchymal transition (EMT, loss of cell adhesion) at tumor invasion
fronts of lung squamous cell carcinoma with the microfluidic probe.
Abstract
Understanding the microenvironment at invasion fronts provides insight into tumor progression,
cellular signaling driving tumor growth and response to chemotherapy. Microscopic lanes of
immunoreactivity for antigens layered in close topographic proximity may facilitate the analysis of
tumor microenvironment (TME) interactors. This project will make use of the Microfluidic Probe
(MFP, a microfluidic technology invented at IBM Research-Zurich [1]) to investigate the relevant
TME-driving proteins at the invasion fronts.
Description
Squamous cell carcinoma (SCC) is a major histologic variant of lung cancer. SCC has a prominent
scarred stroma, which consists of cancer-associated fibroblasts, tumor endothelial cells and diverse
immune cells. SCC cells can infiltrate into their own newly formed stroma by detachment of
cohorts or pushing borders. At the tumor-stroma interface a morphologic and biochemical transdifferentiation occurs, called epithelial–mesenchymal transition. EMT is characterized by an
increase of the intermediate filament Vimentin and the matricellular protein Periostin, paralleled
by a decrease of the cell-adhesion molecule E-cadherin. This process is regulated by transcription
factors such as Slug. These invasion fronts are assumed to be the most chemo-resistant part of a
carcinoma.
Scientists at the Institute of Surgical Pathology, University Hospital Zurich detected Periostin in
malignant pleural effusions by mass spectrometry. In an NSCLC patient cohort, high Periostin
was associated with tumor progression, squamous cell histotype and
decreased survival of lung cancer. Its upregulation occurred mainly at
the invasion front in both tumor epithelia and immediately
surrounding matricellular stroma. From there, a gradual decrease was
observed towards central tumor areas [2]. Similar results were found
for Vimentin, the transcription factor Slug and the cell-adhesion
molecule L1CAM. Conversely, expression of E-cadherin decreased
towards the tumor-stroma interface [3].
The MFP, developed by the IBM group, delivers, adds and subtracts
biomolecules, creates chemical gradients, performs reactions at
biological interfaces and manipulates cell samples in close vicinity of
surfaces. With the MFP, multiplexed (see figure, right) and adaptive
immunostaining was demonstrated [4].
Tasks
We envision the MFP to assess the expression of EMT-related proteins in close topographical
relation of the tumor-invasion front and the matricellular space, respectively. Such investigations
may provide new insight into mechanism and types of invasion.
 You will create microscopic lanes of immunoreactivity of EMT antigens on cell block and
establish metrics for tissue staining.
 You will explore the creation of diverse patterns in orthogonal direction to the invasion front.
 You will create immunostains for Vimentin and Periostin on SSC tissues sections.
Project type
Masters Project
Times frame
6-12 months; starting date is flexible.
Requirements
You must be strong in one of the following disciplines: molecular/cell biology, pathology or
biomedical engineering. You must be motivated, self-driven and keen to work on experiments.
Contact
Prof. Dr. Alex Soltermann (044 255 2319; alex.soltermann@usz.ch) or
Dr. Govind Kaigala (044 724 8929; gov@zurich.ibm.com)
The project will be performed at the Institute of Surgical Pathology, University Hospital and IBM Research – Zurich,
where you will be exposed to an active, vibrant and stimulating research environment.
Further information:
[1] G. Kaigala, R. D. Lovchik, U. Drechsler and E. Delamarche, Langmuir, 27, 5686, 2011.
[2] A. Soltermann et al., Clinical Cancer Research, 14, 7430-7437, 2008.
[3] V. Tischler et al., Molecular Cancer, 10, 127, 2011.
[4] R.D. Lovchik, G.V. Kaigala, M. Georgiadis, E. Delamarche, Lab Chip, 12, 1040, 2012.