Effects Of NCAM On The Morphology, Growth And Motility Of Tumor Cells

Neural cell adhesion molecule(NCAM), a kind of glycoproteins expressing on the cell surface, which belongs to the immunoglobulin superfamily, engages in both cell-cell and cell-extracellular matrix adhesion. It also influences migration and proliferation of nervous system cells and synaptic plasticity. Polysialic acid(PSA), a linear homopolymer composed of α-2, 8-linked sialic acid residues, is exclusively attached to NCAM. Biosynthesis of PSA is catalyzed by polysialyltransferases, ST8 Sia IV(PST) and ST8 Sia II(STX). They are responsible for modification of NCAM on the fifth and sixth N-glycosylation sites. PSA is aberrantly re-expressed in many malignan tumors,such as non-small cell lung cancer, neuroblastoma and wilms tumor. PSA-NCAM takes efforts on the identification, infiltration and growh of tumors.Epithelial to mesenchymal transition(EMT) is essential for embryonic development, which plays a critical role in progression of tumor migration and invasion. Normal cells can undergo EMT induced by transforming growth factor β(TGF-β).This study investigated the effects of NCAM on cell morphology, growth and motility using the normal epithelial cell line and mammary cancer cell line. NCAM and PSA-NCAM could mediate EGFR and STAT3 signal pathway. This study suggested NCAM and PSA-NCAM played important roles in breast cancer.First, NCAM expression was compared in normal breast cells and malignant breast tumor cells. It was detected that the expression level of NCAM in malignant breast cancer cells was higher than normal breast cells. When normal breast cells underwent EMT induced by TGF-β, NCAM expression was up regulated.Normal breast cells MCF10 A were stably transfected with NCAM-140, reduced E-cadherin expression, increased N-cadherin expression. Cell displayed enhanced motility, proliferation was not changed. Besides, EGFR and STAT3 signal pathways were activated. The same changes were confirmed in MCF7 cells over-expressed NCAM-140. Results showed NCAM could promote EMT process. Free sialic acids were detected by HPLC. Results showed the expression level of sialic acids in malignant breast tumor cells were higher than in normal breast cells. Breast tumor cells MCF7 were transiently transfected with NCAM-140 and polysialyltransferases PST and STX. NCAM and PSA-NCAM could activate EGFR and STAT3 signal pathways. MCF10 A cells were transiently transfected with the mutant plasmids of the 5th and 6th N-glycosylation sites of NCAM-140. NCAM that was removed of PSA could activate EGFR and STAT3 signal pathways. These data demonstrated that NCAM that was independent of PSA could promote EMT process via EGFR and STAT3 signal pathways. NCAM played an important role in occurrence and development of breast cancer.