Cell News 04/2018
26
MEETING REPORT
In the final presentation before lunch,
Tomasz Zielinski
(Polish
Academy of Sciences) presented a thorough examination of
how glioblastoma cell biomechanics react to disruption of the
actin cytoskeleton. Specifically, AFM indentation measure-
ments showed that fibroblast-like glioblastoma cells become
more deformable after treatment with Cytochalasin D while
their keratinocyte-like counterparts actually become stiffer.
This was hypothesized to be connected to the disruption of me-
chanically supportive stress fibers in fibroblast-like glioblasto-
ma cells, while their absence in keratinocyte-like glioblastoma
cells leads to the opposite effect.
After lunch break, the sixth session with an emphasis on cancer
and embryology started off with a talk by
Benjamin Wolf
from
Leipzig University Hospital. In his presentation, he challenged
the current understanding of local tumor spread as an isotro-
pic process. He showed evidence from clinical data and from
computer simulations indicating that the local propagation of
cervical cancer follows a predictable pathway and argued that
this concept can be used to tailor tissue resection precisely
according to risk and thus minimize comorbidity by sparing
functionally important low-risk tissues while maximizing
oncological benefit. He concluded his presentation by showing
images from orthotopic tumor transplantation experiments
which are currently carried out to investigate the propensity of
cervical cancer to infiltrate various healthy tissues.
In the next presentation,
Maryam Aliee
from FAU Erlangen
shared results from tissue growth modelling and showed how
a continuum model taking into account cell mechanics and
growth can be used to study the differentiation of MDCK cells
into a primitive tissue consisting of a central immobile region
and a looser outer cellular rim. In addition, she presented data
showing how two tissue types with different homeostatic
pressures are segregated by an interface driven by the pressure
difference, and how this process can be described by using a
generalized form of the Fisher wave equation.
Sui Huang
from the Institute for Systems Biology contin-
ued with a fascinating talk how emerging drug resistance in
cancer patients treated with chemotherapy can be described
as the transition of a cell from one stabile high-dimension-
al gene expression state (referred to attractor) into another.
Interestingly, this concept of drug resistance does not require
genetic mutations to explain phenotypic alterations but rather
describes cell state transitions as the movement of cells in a
high-dimensional gene expression state space in which some
expression states are more stable (attractors). Environmental
stress such as chemotherapy can lower the energy barrier
which has to be overcome in order to move from one attractor
state to another. While cancer treatment aims at moving cells
into a desirable attractor state (i.e. apoptosis), it can backfire
by leading to cells to the occupation of a less desirable attrac-
tor (i.e. conferring drug-resistance). He supported the concept
with intriguing data from single cell resolution gene expression
profile measurements and showed how critical transcription
state transitions are preceded by early warning signals herald-
ing the emergence of “rebellious cells” entering an alternative,
“undesirable” attractor state.
The session concluded with a contributed talk by
Christoph
Mark
from FAU Erlangen who showed that the invasion of
adjacent environments by cell collectives such as tumor spher-
oids occurs by collective exertion of forces on the surround-
ing matrix. He shared results from recent experiments with
glioblastoma spheroids using a novel assay, which exploits the
spherical symmetry of tumor spheroids to derive a scale-invari-
ant relation between spheroid contractility and the surrounding
matrix deformations. Using this technique, he showed that only
during the initial phase of tumor invasion, the collective force
of a spheroid reflected the forces exerted by the single cells.
Interestingly, the large forces straining the extracellular fiber
network may significantly alter the mechanical microenviron-
ment (more than a single cell could do), therefore inducing
more favorable conditions for further invasion.
The last session of the conference was dedicated to transla-
tional research and began with a presentation by
Ivonne Nel
from Leipzig University Hospital. She explained how tumor cells
egress from primary breast cancer sites at early tumor stages to
remain in dormancy for many years at distant sites (preferably
the bone marrow) until they can cause disease recurrence and
metastasis many years after treatment of the primary cancer.
She moved on to demonstrate how immunohistochemical
methods can be used to detect disseminated tumor cells in
bone marrow aspirates and discussed how characterization of
these cells might be useful as a prognostic marker. She con-
cluded her talk by showing promising data on how disseminat-
ed tumor cells could be eradicated by bisphosphonates.
The conference concluded with a final invited talk by
Roberto
Osellame
from the Institute for Photonics and Nanotechnol-
ogy in Milano. After a quick introduction about the role of
optofluidic devices for single cell characterization in general,
he presented novel devices combining microfluidic and optical
technologies in monolithic chips, enabling high-throughput
synchronous mechanical and immunofluorescent single cell
analysis and sorting. During the discussion it became clear how
advantageous an unbiased cell characterization approach such
as mechanical phenotyping can be, and how applicable this
high-throughput approach might be in various clinical scenarios.
After final remarks by
Josef Käs
, some participants joined the
organizers for an informal farewell burger at “Hans im Glück”,
just opposite the conference venue in downtown Leipzig.
Feedback from participants was very positive, and most showed
interest in joining the POC symposium next year, which will be
the 10th. For more information and early registration, please
visit
.
