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Interactions between human colon carcinoma cells, fibroblasts and monocytic cells in coculture--regulation of cathepsin B expression and invasiveness.

Krueger S, Kalinski T, Wolf H, Kellner U, Roessner A

Department of Pathology, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany. sabine.krueger@medizin.uni-magdeburg.de

To elucidate the importance of the tumor/host interaction in malignant tumors, we investigated the colon carcinoma cell line HT-29 in coculture with monocytic cells (THP-1) and fibroblasts (175BR) for cathepsin B expression and activity. The tumor cells were grown in monolayer cultures or as multicellular tumor spheroids. After coculture, the three cell types were separated by labeled magnetic beads for cathepsin B mRNA and protein analysis. The invasive potential was studied in in vitro invasion assays. The expression level of cathepsin B was found to be 10-fold increased in three dimensional spheroids of HT-29 compared to HT-29 monolayers. The coculture of HT-29 with THP-1 cells and/or human fibroblasts led to a considerable increase in cathepsin B mRNA expression in both tumor and tumor-associated cells. The invasive potential of the tumor cells was 5 times increased by adding monocytic cells to the assay system. This is dependent on the functional activity of cathepsin B as shown by specific siRNA's and seems to be regulated by activation of ERK1/2 and p38 signal transduction pathways.

Published 17 May 2005 in Cancer Lett, 223(2): 313-22.
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