This work aimed to use controlled engineered cell environments to improve the understanding of the role of external cues on drug response. We used a microwell array, previously developed in our group , which enables the culture of cells in a 3D environment with control of cell cluster size down to the single cell level. It also allows the control of the biochemical interface with the cells. Initially we studied the influence of
dimensionality on the response to taxol on the breast carcinoma cell line, MCF-7. Cancer cells cultured in microwells showed an increased resistance to taxol in comparison to cells cultured on flat substrates. A similar change in drug response was observed for cells in cell-derived fibronectin matrices. These results in two 3D systems,
of different complexity, LCZ696 ic50 demonstrate that dimensionality is an important factor for determining the responsiveness of cells to drugs. In addition, the results showed that the microwell array can be used as an in vivo mimic, and is therefore a promising tool for the screening of MK5108 cell line anti-cancer drugs. References: 1. Bissell, M. J., Differentiation, 70, 537–546, 2002. 2. Serebriiski et al., Matrix Biology, 27, 1074–1077, 2007. 3. Aoudjit, F. et al., Oncogene, 20, 4995–5004, 2001. 4. Ochsner, M. et al., Lab Chip, 7, 1074–1077, 2007. Poster No. 149 FAP-positive Fibroblasts Express FGF1 and Increases OSI-027 price Migration and Invasion of Colon Cancer Cells Maria L. Henriksson 1 , Sofia Edin1, Anna M. Dahlin1, Per-Arne Oldenborg2, Åke Öberg3, Bethany Van Guelpen1, Jörgen Rutegård3, Roger Stenling1, Richard Palmqvist1 1 Department of Medical Biosciences/Pathology, Umeå Universtiy, Umeå, Sitaxentan Sweden, 2 Department of Integrative Medical Biology, Section for Histology and Cell Biology, Umeå Universtiy, Umeå,
Sweden, 3 Department of Surgical and Perioperative Sciences, Surgery, Umeå Universtiy, Umeå, Sweden Background: Colorectal cancer is one of the leading causes of cancer deaths in western countries, with death generally resulting from metastatic disease. In recent years, the importance of the tumor microenvironment, including tumor-associated fibroblasts, has paid increasing attention. Aim: To analyze the effect of Fibroblast activation protein (FAP)-expressing fibroblasts on colon cancer cell migration and invasion in experimental cell studies. We also investigated the expression pattern of FAP in tumor-associated fibroblasts during transformation from benign to malign colorectal tumors. Methods and results: In immunohistochemical analyses, FAP was expressed in fibroblasts in all carcinoma samples examined (n = 61), whereas all normal colon (n = 12), hyperplastic polyps (n = 16) or adenoma (n = 55) samples were negative for FAP. In in vitro studies, conditioned medium from HCT-116 colon cancer cells, but not LT97 adenoma cells, induced FAP expression in colon fibroblasts.