Abstract
We have previously shown that certain gliomas expressed procollagen type1 alpha1(1α1). Procollagen is synthesized in the endoplasmic reticulum, modified and packaged in the Golgi body and transported out of the cells. Once exited, the N-and C-terminal are cleaved by peptidase and fibril is formed. The collagen can interact with integrin, Endo180, or discoindin domain receptor(DDR). DDR is a class of receptor tyrosine kinase. The binding to collagen triggers autophosphorylation of DDR and initiation of other signaling cascades which are poorly understood, but have been implicated for cellular proliferation and invasion. DDR is comprised of 2 members(DDR1 and DDR2). Thus far, the clinical relevance of this pathway is not known. However, DDR1 has been reported in glioblastoma multiforme, both in cell lines and tissue and correlates with poor prognosis. In this report, w
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investigated the expression of procollagen1α1, DDR1 and DDR2 in 6 glioma cell lines. Silencing procollagen1α1, DDR1 or DDR2 resulted in impairment of cell migration. Silencing procollagen1α1 resulted in cell cycle arrest at G2/M. This effect is less when silencing DDR1 or DDR2. However, silencing DDR1 or DDR2 resulted in attenuation of pERK and pAKT. Since there is no inhibitor of collagen or DDRs, we have used Brefeldin A, which can block procollagen secretion out of the cell.
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reatment with Brefeldin A resulted in retention of procollagen in the ER. Thus, less procollagen was secreted and hence there was less ligand to bind DDRs. As a result, less DDRs were activated. Our data suggest that there is a definite relationship between collagen and DDRs in gliomas which can affect cellular proliferation and migration. The downstream of this signaling is not yet understood but it can be explored for future treatment of glioma which possess both the ligand and receptor.
