TY  - JOUR
A1  - Hofmann, Matthias
A1  - Guschel, Maike
A1  - Bernd, August
A1  - Bereiter-Hahn, Jürgen
A1  - Kaufmann, Roland
A1  - Wiig, Helge
A1  - Kippenberger, Stefan
T1  - Lowering of tumor interstitial fluid pressure reduces tumor cell proliferation in a xenograft tumor model
T2  - Neoplasia
N2  - High tumor interstitial fluid pressure (TIFP) is a characteristic of most solid tumors. TIFP may hamper adequate uptake of macromolecular therapeutics in tumor tissue. In addition, TIFP generates mechanical forces affecting the tumor cortex, which might influence the growth parameters of tumor cells. This seems likely as, in other tissues (namely, blood vessels or the skin), mechanical stretch is known to trigger proliferation. Therefore, we hypothesize that TIFP-induced stretch modulates proliferation-associated parameters. Solid epithelial tumors (A431 and A549) were grown in Naval Medical Research Institute nude mice, generating a TIFP of about 10 mm Hg (A431) or 5 mm Hg (A549). Tumor drainage of the central cystic area led to a rapid decline of TIFP, together with visible relaxation of the tumor cortex. It was found by sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blot analysis that TIFP lowering yields a decreased phosphorylation of proliferation-associated p44/42 mitogen-activated protein kinase and tumor relaxation. In confirmation, immunohistochemical staining showed a decrease of tumor-associated proliferation marker Ki-67 after TIFP lowering. These data suggest that the mechanical stretch induced by TIFP is a positive modulator of tumor proliferation.
KW  - Tumor interstitial fluid pressure
KW  - tumor cell proliferation
KW  - mechanical stimuli
KW  - p44/42 MAPK
KW  - Ki-67
Y1  - 2006
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/55106
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-551062
SN  - 1522-8002
SN  - 1476-5586
N1  - Under a Creative Commons license
VL  - 8
IS  - 2
SP  - 89
EP  - 95
PB  - Stockton Press
CY  - Basingstoke
ER  -