PoC - Physics of Cancer - Annual Symposium
Poster, Friday, 19:00  
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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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] 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).
[2] 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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