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Poster, Friday, 19:00 |
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Some observations on the growth
of tumors in hydrogel environments
Kristen L. Mills, Krishna Garikipati,
Ralf Kemkemer
Max Planck Institute for Intelligent
Systems, Biomaterials, Heisenbergstraße 3, 70569 Stuttgart, Germany |
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Contact:
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One of the “hallmarks” of cancer is uninhibited cellular proliferation
resulting in growth. The unregulated growth consequentially forces a solid
tumor to mechanically interact with its surrounding tissues in physiologically
atypical and, oftentimes, catastrophic ways. It is therefore important
to understand the effects of the environment on the growth as well as how
the growth effects the environment. Previous studies have indicated that
increased compressive pressure due to growth alone could be responsible
for phenotypic alterations in cancer cells [1] and blood-vessel collapse
that would block nutrients to the native tissue or anti-cancer drug delivery
to the tumor [2].
As the experimental part of a joint experimental-theoretical study
aimed at directly comparing the most essential processes of tumor growth
(bio-chemo-mechanical) using their rates of free energy change during growth,
we study the growth and shape changes of tumors in nonadhesive hydrogel
environments differing in stiffness. In the non-adhesive environment, the
tumors take on an oblate or lens-like shape that has received little attention
until now. We have determined that the oblate shape likely develops due
to multiple factors including more compliant planes in the hydrogel, a
competition between the cells for nutrients, and multiple populations of
cells with different rates of proliferation. The pressure induced by the
volumetric strain created by the growing tumor spheroids dictates plateau
growth of the tumors. The factors affecting this not only include hydrogel
stiffness but also the density of tumors embedded in the hydrogel. These
results shed light on growth and diffusion processes of solid tumors.
[1] |
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G. Cheng, J. Tse, R. K. Jain, L. L.
Munn: Micro-environmental mechanical
stress controls tumor spheroid size and morphology by suppressing proliferation
and inducing apoptosis in cancer cells, PLoS ONE, 4(2): e4632 (2009). |
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[2] |
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G. Helmlinger, P. A. Netti, H. C. Lichtenbeld,
R. J. Melder, R. K. Jain: Solid
stress inhibits the growth of multicellular tumor spheroids, Nature
Biotechnology, 15(8): 778-783 (1997). |
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