E-cadherin-dependent intercellular adhesion enhances chemoresistance

Int J Mol Med. 2003 Nov;12(5):693-700.

Abstract

E-cadherin, an intercellular adhesion molecule, is important in cell growth and differentiation. Adhesion between cells is thought to decrease as cancers develop and disseminate. Knowledge of the effect of cell adhesion on proliferation and chemosensitivity may help individualize cancer treatment. Lovo and MCF-7 cells, which express E-cadherin, and PC-3 cells, which do not, were used in this study. Proliferation and chemosensitivity were measured in two-dimensional (2-D) culture and three-dimensional (3-D) culture. Protein and mRNA expression of E-cadherin, catenin, and cyclin-dependent kinase inhibitors were determined. Growth of Lovo and MCF-7 but not PC-3 cells was markedly suppressed in 3-D relative to 2-D. MCF-7 cells express high levels for E-cadherin, catenin, and p27 in 3-D, but catenin and p27 expression was decreased by exposure to anti-E-cadherin neutralizing antibody. Chemosensitivity of PC-3 was similar in 2-D and 3-D, but chemosensitivity of Lovo and MCF-7 was less in 3-D than 2-D. Moreover, the presence of anti-E-cadherin antibody increased chemosensitivity of MCF-7 in 3-D. E-cadherin affected the regulation of cell proliferation and differentiation, and decreased chemosensitivity. Chemosensitivity of cancer is affected by the state of cell adhesion and expression of intercellular adhesion molecules. Consideration of intercellular adherence characteristics in different chemosensitivity tests is likely to improve their reliability.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Apoptosis / drug effects
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Cell Adhesion / drug effects
  • Cell Cycle Proteins / antagonists & inhibitors
  • Cell Cycle Proteins / metabolism
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Cell Size
  • Cisplatin / pharmacology
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinase Inhibitor p57
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Cyclins / antagonists & inhibitors
  • Cyclins / metabolism
  • Cytoskeletal Proteins / metabolism
  • Doxorubicin / pharmacology
  • Drug Resistance, Neoplasm*
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology
  • Fluorouracil / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Mitolactol / pharmacology
  • Mitomycins / pharmacology
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Trans-Activators / metabolism
  • Tumor Suppressor Proteins / antagonists & inhibitors
  • Tumor Suppressor Proteins / metabolism
  • alpha Catenin
  • beta Catenin

Substances

  • CDKN1A protein, human
  • CDKN1C protein, human
  • CTNNA1 protein, human
  • CTNNB1 protein, human
  • Cadherins
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinase Inhibitor p57
  • Cyclins
  • Cytoskeletal Proteins
  • Enzyme Inhibitors
  • Mitomycins
  • Nuclear Proteins
  • RNA, Messenger
  • Trans-Activators
  • Tumor Suppressor Proteins
  • alpha Catenin
  • beta Catenin
  • Cyclin-Dependent Kinase Inhibitor p27
  • Doxorubicin
  • Cyclin-Dependent Kinases
  • Mitolactol
  • Cisplatin
  • Fluorouracil

Supplementary concepts

  • ADM protocol