Synthetic (glyco-)peptides of the homophilic recognition domain of E-cadherin lead to increased E-cadherin mRNA synthesis and are inductors of cell differentiation in primary lung cancer cell lines.
E-cadherin is one of the critical molecules involved in the metastatic process in many types of cancer. Once combined, E-cadherin exceeds the amount of membranous E-cadherin on the cellular surface by activation of intracellular signaling cascades. Studies on transformed keratinocytes of the HaCat cell line showed induction of differentiation by synthetical partial structures of the homophilic binding region of E-cadherin. The knowledge of effects in lung cancer cells is sparse. Therefore, the effects in primary lung cancer cell lines were investigated. Four primary lung cancer cell lines were incubated for 3, 6, 12, 15, 18, and 24h with synthetic partial structures (peptide and glycopeptide). The control substance was sodium butyrate. mRNA was isolated, and relative quantification of E-cadherin was performed using the Real-Time PCR. During the stimulation period, morphologic pictures were taken, and immunohistochemical staining of membranous E-cadherin was performed. Life/dead assays were used to display cell vitality. The intracellular E-cadherin mRNA amount was increased after incubation with the synthetic partial structures. Life/dead assays showed improved survival and integrated cell/cell bindings after stimulation with the partial structures. Increased cell mortality was revealed after sodium butyrate incubation. An effect mediated via E-cadherin on the cellular surface is proposed. The two synthetic partial structures of the homophilic binding region of E-cadherin increased the intracellular E-cadherin mRNA amount, cell-cell bindings, and survival of the tumor cells. Extracellular binding by synthetic partial structures to the binding region may have a beneficial influence on tumor progression in the metastatic process.
Zeckey
Christian
C
Department of Cardio-Thoracic and Vascular Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Germany. Zeckey.Christian@mh-hannover.de
Dahm
Manfred
M
Wallrath
Anja
A
Herr
Monika
M
Walter Kunz
Horst
H
Vahl
Christian-Friedrich
CF
Horn
Sigrid
S
D015820:Cadherins / Q000737:chemistry / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D006020:Glycopeptides / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015820:Cadherins; D006020:Glycopeptides; D012333:RNA, Messenger