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| Invited Talk, Saturday, 09:45 – 10:15 |
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| Exploring the impact of cell
mechanics on cancer progression with the Microfluidic Optical Stretcher
Mareike Zink1, Franziska
Wetzel1, Anatol Fritsch1, Steve Pawlizak1,
Tobias Kießling1, K. David Nnetu1, Lars-Christian
Horn2, Michael Höckel3, Josef A. Käs1
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1
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Soft Matter Physics Division, Institute
of Experimental Physics I, University of Leipzig, Linnéstraße
5, 04103 Leipzig, Germany |
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2
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Division of Breast, Gynecologic
& Perinatal Pathology, Institute of Pathology, University of Leipzig,
Liebigstraße 26, 04103 Leipzig, Germany |
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3
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Department of Obstetrics and Gynecology,
Medical
School, University of Leipzig, Liebigstraße 20a, 04103 Leipzig, Germany |
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| Contact:
| Website |
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Biophysics established a new research area which described the progression
of cancer from a materials science perspective. It has been know for a
long time that malignant transformation is associated with significant
changes in the cellular cytoskeleton. If the cytoskeleton’s alterations
are necessary for malignant transformation, they have to trigger biomechanical
changes that impact cellular functions. In all cancers malignant neoplasia
– uncontrolled growth, invasion into the surrounding tissue and metastasis
occurs. Our results indicate that all these three phenomechanisms of malignancy
require changes in the active and passive biomechanics of a tumor cell.
Microfluidic Optical Stretcher (MOS) experiments with tumor cell lines
clearly show that malignant transformation causes cell softening for small
deformations which correlates with an increased rate of proliferation compared
to normal cells. Additionally, three clinical studies were carried out
to prove the potential of the MOS for cancer diagnosis. First, primary
oral squamous carcinoma cells from patients with early dysplasia and malignant
tumors were probed with the MOS and compared with the deformability of
primary oral cells from healthy donors. Second, breast tumor cells were
resected from the women’s body and deformed within the MOS together with
primary normal breast epithelial cells. Third, primary cervical carcinoma
cells and normal epithelial cells resected from the same morphological
compartment of the same women were examined. From all experiments we clearly
found that tumor cells are softer compared to normal cells and exhibit
a broader distribution of optical deformability. Since cell softening during
malignant transformation seems to be a universal behavior of tumor cells,
the MOS offers the possibility to detect many different types of tumors
without any further knowledge of the molecular details of the cells. Furthermore,
cell softening of the actin cortex can increase individual cell speed for
lamellipodial motion of malignantly transformed cells. However, all cells
can migrate and the motion of epithelial cells is mainly determined by
their environment, whereas fibroblasts have the capability to move freely.
Thus, it is the ability of single epithelial cells to overcome the tumor
barrier to metastasize. The barrier that cells feel when they try to leave
their cell compartment can be lowered by reducing cell-cell adhesion which
was studied with CellHesion scanning force microscopy. |
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