We therefore investigated, by immunohistochemistry, the potential prognostic and response predicative PKC412 price roles of stromal PDGF receptors in breast cancer. In a population-based cohort of breast cancers we found associations between PDGF β-receptor status and clinico-pathological characteristics. High stromal PDGFβ-receptor expression was significantly associated with high histopathological grade, ER negativity and high HER2 expression. High stromal PDGF β-receptor expression also correlated with significantly shorter recurrence-free and breast cancer specific
survival. The prognostic significance of stromal PDGF β-receptor expression was particularly prominent in tumors from pre-menopausal women. In an independent material, derived from a phase III study of adjuvant tamoxifen, we find more analyzed the response-predicative role of stromal PDGF β-receptor expression. When patients were divided according to stromal PDGF receptor
expression, it was noted that the therapeutic benefit of tamoxifen was much more prominent in the group with low stromal PDGF receptor expression. These results suggest a previously unrecognized response-predicative role of stromal PDGF β-receptor in breast cancer. The mechanistic basis for this phenomenon is currently explored in co-culture experiments where the potential Selleck Evofosfamide PDGF-dependent influence of fibroblasts on breast cancer cell sensitivity to tamoxifen is being analyzed. In summary our studies indicated novel prognostic and response-predicative roles of stromal PDGF receptor expression, which should be explored in the continued development of PDGF receptor inhibitors and endocrine treatments. Poster No. 99 Co-Cultured Fibroblasts Regulate Colorectal Cancer Cell Proliferation, Migration, Invasion and Cetuximab-Sensitivity in a PDGF- dependent Manner Cristina Peña 1 , Maja Bradic Lindh 1, Arne Östman1 1 Department of Pathology-Oncology,
Karolinska Institutet, Stockholm, Solna, Sweden PDGF tyrosine kinase receptors activation has been involved in multiple aspect Methocarbamol of cancer growth. In solid tumors PDGF receptor signaling appears to be most important for the pericytes and fibroblasts of the tumor stroma. We have developed co-culture assays to analyze the paracrine interactions between fibroblasts (PDGFR+) and colorectal cancer (CRC) cells (PDGFR-). PDGF-dependent effects of fibroblasts on the proliferation, migration, invasion and response to EGFR inhibitor (Cetuximab) of CRC cells (HT29, SW620 and LIM1215) were analyzed in different co-culture models. PDGF stimulation of fibroblasts increased the migration and invasion of LIM1215 and HT29 CRC cells. The fibroblast-induced migration of SW620 cells, which produce PDGFs, could be blocked by PDGF receptor inhibitors targeting the co-cultured fibroblasts. Furthermore, “priming” of matrigel with fibroblasts indicated PDGF-dependent effects on the matrigel which facilitated CRC cell invasion.