Tumor-stroma interaction of human pancreatic cancer: acquired resistance to anticancer drugs and proliferation regulation is dependent on extracellular matrix proteins

Pancreas. 2004 Jan;28(1):38-44. doi: 10.1097/00006676-200401000-00006.


Introduction: 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.

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

Methodology and 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.

Conclusion: 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.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Division / drug effects
  • Cell Line, Tumor / drug effects
  • Cell Survival / drug effects
  • Cisplatin / pharmacology
  • Collagen Type I
  • Collagen Type IV / pharmacology
  • Doxorubicin / pharmacology
  • Drug Interactions
  • Drug Resistance, Neoplasm
  • Extracellular Matrix Proteins / pharmacology*
  • Fibronectins / pharmacology
  • Fluorouracil / pharmacology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Integrins / genetics
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism


  • Antineoplastic Agents
  • Collagen Type I
  • Collagen Type IV
  • Extracellular Matrix Proteins
  • Fibronectins
  • Integrins
  • RNA, Messenger
  • Doxorubicin
  • Cisplatin
  • Fluorouracil