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P53 mutations in stromal fibroblasts sensitize tumors against chemotherapy
Author(s) -
Lafkas Daniel,
Trimis George,
Papavassiliou Athanasios G.,
Kiaris Hippokratis
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23546
Subject(s) - stromal cell , paracrine signalling , cancer research , chemotherapy , carcinogenesis , doxorubicin , stroma , cancer associated fibroblasts , prostate cancer , medicine , biology , prostate , senescence , breast cancer , cancer , cancer cell , oncology , pathology , receptor , immunohistochemistry
The efficacy of chemotherapy is usually viewed as the outcome of cancer‐cell‐autonomous processes while the contribution of stroma is being overseen. Here we show that p53 mutations in stromal fibroblasts, a genetic lesion that is detectable in primary breast, prostate and probably other cancers, while they accelerate tumorigenesis they also sensitize tumours against conventional chemotherapy by doxorubicin and cis ‐platinum. The mechanism by which p53 of stromal fibroblasts affects the response of a tumour against chemotherapy is likely to involve the induction of senescence in the fibroblasts which in turns results in the production of growth factors acting onto the cancer cells by paracrine mechanisms. Our findings identify stromal fibroblasts as important modulators of the efficacy of anticancer therapy. © 2008 Wiley‐Liss, Inc.