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


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.


CONCLUSIONS
3-D collagen cell culture systems can be used to study cancer cell potential for invasion and their relative sensitivity/resistance to anticancer drugs.
Oncology and Molecular Endocrinology Research Center, CHUL's Research Center, CHUQ, 2705 boul. Laurier, Quebec City, Québec G1V 4G2, Canada. Charles.doillon@crchul.ulaval.ca
Charles J
CJ
Doillon
Edith
E
Gagnon
Renée
R
Paradis
Michael
M
Koutsilieris
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology; D002945:Cisplatin / Q000494:pharmacology; D003094:Collagen; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000473:pathology; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005337:Fibrin; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D008297:Male; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D014407:Tumor Cells, Cultured
D004317:Doxorubicin; D005337:Fibrin; D003094:Collagen; D017239:Paclitaxel; D002945:Cisplatin