Tumor-stroma interaction of human pancreatic cancer: acquired resistance to anticancer drugs and proliferation regulation is dependent on extracellular matrix proteins.
BACKGROUND
Pancreatic cancer is one of the major causes of cancer-related deaths in industrialized countries. It is known that pancreatic cancer is resistant to chemotherapy and that cancer cells are surrounded by extracellular matrix (ECM) proteins including collagen I, collagen IV, fibronectin, and laminin.


OBJECTIVE
To examine the role of ECM proteins in acquired resistance to anticancer drugs and proliferation regulation in pancreatic cancers.


RESULTS
We used an in vitro model of ECM-induced chemoresistance and cell proliferation of cancer cell lines (MIA PaCa-2, PANC-1, and Capan-1) with 3 different malignancy grades and found that resistance to cytotoxic drugs and proliferation regulation was dependent on ECM proteins. Pancreatic cancer cell lines, especially MIA PaCa-2 cells, adhering to any of the ECM proteins showed decreased cytotoxicity of anticancer drugs, except for gemcitabine. PANC-1 and Capan-1 cells adhering to fibronectin, collagen I, and collagen IV proliferated more than the controls.


CONCLUSIONS
ECM proteins have important roles in acquired resistance to anticancer drugs and cell proliferation regulation of pancreatic cancer cells. Therefore, the expression of ECM proteins in pancreatic cancer specimens could provide valuable information to aid anticancer drug cytotoxicity, and gemcitabine would be useful for treatment of patients with pancreatic cancer.
Miyamoto
Hidenori
H
Department of Digestive Surgery, The University of Tokushima School of Medicine, Tokushima, Japan. h.miya-k@komagome-hospital.bunkyo.tokyo.jp
Murakami
Tatsuya
T
Tsuchida
Kunihiro
K
Sugino
Hiromu
H
Miyake
Hidenori
H
Tashiro
Seiki
S
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D024042:Collagen Type I; D024141:Collagen Type IV / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm; D016326:Extracellular Matrix Proteins / Q000494:pharmacology*; D005353:Fibronectins / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016023:Integrins / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D024042:Collagen Type I; D024141:Collagen Type IV; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D016023:Integrins; D012333:RNA, Messenger; D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil