Three-dimensional culture system as a model for studying cancer cell invasion capacity and anticancer drug sensitivity.

Abstract

BACKGROUND: Three-dimensional (3-D) culture systems that simulate the tumor extracellular microenvironment may be appropriate to test cancer cell potential for invasion and tumor cell sensitivity to anticancer drugs. MATERIALS AND METHODS: Human PC-3 prostate, A549 colon, HT-29 lung and MCF-7 and MDA-MB231 breast cancer cells were embedded and grown in collagen gel surrounded by a fibrin clot. Increasing concentrations of cisplatin, doxorubicin, paclitaxel and 5-fluorouracil were comparatively evaluated for their ability to inhibit tumor cell proliferation and colony formation in vitro. RESULTS: All cells, except MDA, formed colonies in collagen. PC-3, A549 and HT-29 cells massively invaded fibrin forming migratory fronts. Cell colonies were also formed in fibrin (secondary tumor-like structures) apart from migratory fronts; HT-29 cells were the most aggressive in this regard MDA cells were particularly sensitive to doxorubicin, while MCF-7 cells showed sensitivity to all anticancer regimens tested. A549 cells were the tumor cell type with greatest potential for invasion and were sensitive mostly to cisplatin. PC-3 cells were primarily sensitive to cisplatin and doxorubicin, while HT-29 cells were sensitive to fluorouracil and doxorubicin. CONCLUSION: 3-D collagen cell culture systems can be used to study cancer cell potential for invasion and their relative sensitivity/resistance to anticancer drugs.