Highly variable response to cytotoxic chemotherapy in XXXX -associated fibroblasts (CAFs) from lung and breast.

@entity1 @entity11833 @entity0 @entity5 @entity7465 @entity900 @entity1311 @entity189 @entity2 @entity876 @entity105
BACKGROUND: @entity189 -associated fibroblasts (CAFs) can promote @entity105 and @entity5 progression. Only limited data on the response of CAFs to chemotherapy and their potential impact on therapy outcome are available. This study was undertaken to analyze the influence of chemotherapy on @entity189 -associated fibroblasts (CAFs) in vitro and in vivo. METHODS: The in vivo response of stromal cells to chemotherapy was investigated in 22 neoadjuvant treated @entity0 on tissue sections before and after chemotherapy. Response to chemotherapy was analyzed in vitro in primary cultures of isolated CAFs from 28 @entity1 lung and 9 @entity0 tissues. The response was correlated to @entity7465 , @entity11833 and @entity876 polymorphisms and @entity876 mutation status. Additionally, the cytotoxic effects were evaluated in an ex vivo experiment using cultured tissue slices from 16 lung and 17 @entity0 specimens. RESULTS: Nine of 22 @entity5 showed a therapy-dependent reduction of stromal activity. Pathological response of @entity5 or stroma cells did not correlate with clinical response. Isolated CAFs showed little sensitivity to @entity1311 . In contrast, sensitivity of CAFs to @entity900 was highly variable with a GI50 ranging from 2.8 to 29.0 microM which is comparable to the range observed in @entity5 cell lines. No somatic @entity876 mutation was detected in any of the 28 CAFs from @entity2 tissue. In addition, response to @entity900 was not significantly associated with the genotype of @entity876 nor @entity7465 and @entity11833 polymorphisms. However, we observed a non-significant trend towards decreased sensitivity in the presence of @entity876 variant genotype. In contrast to the results obtained in isolated cell culture, in tissue slice culture @entity0 CAFs responded to @entity1311 within their microenvironment in the majority of cases (9/14). The opposite was observed in @entity2 tissues: only few CAFs were sensitive to @entity900 within their microenvironment (2/15) whereas a higher proportion responded to @entity900 in isolated culture. CONCLUSION: Similar to @entity5 cells, CAF response to chemotherapy is highly variable. Beside significant individual/intrinsic differences the sensitivity of CAFs seems to depend also on the @entity5 as well as the microenvironment.
