Blockade of phospholipid scramblase 1 with its N-terminal domain antibody reduces tumorigenesis of colorectal carcinomas in vitro and in vivoReportar como inadecuado




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Journal of Translational Medicine

, 10:254

Combination strategies

Abstract

BackgroundMembrane-bound phospholipid scramblase 1 PLSCR1 is involved in both lipid trafficking and cell signaling. Previously, we showed that PLSCR1 is overexpressed in many colorectal carcinomas CRCs. In the present study, we investigated the tumorigenic role of PLSCR1 in CRC and suggest that it is a potential therapeutic target.

MethodsTo identify PLSCR1 as a therapeutic target, we studied the tumorigenic properties of CRC cell lines treated with a monoclonal antibody NP1 against the N-terminus of PLSCR1 in vitro and in vivo. We also investigated cell cycle status and epidermal growth factor receptor–related pathways and downstream effectors of PLSCR1 after blocking its function with NP1.

ResultsTreating CRC cells with NP1 in vitro and in vivo decreased cell proliferation, anchorage-independent growth, migration, and invasion. Adding NP1 to the CRC cell line HT29 caused arrest at G1-S. Treating HT29 cells with NP1 significantly decreased the expression of cyclin D1 and phosphorylation levels of Src, the adaptor protein Shc, and Erks. The reduced level of cyclin D1 led to an increase in the activated form of the tumor suppressor retinoblastoma protein via dephosphorylation. These actions led to attenuation of tumorigenesis.

ConclusionsTherefore, PLSCR1 may serve as a potential therapeutic target for CRC.

KeywordsPhospholipid scramblase 1 Retinoblastoma dephosphorylation Cyclin D1 Cell cycle G1-S arrest Colorectal carcinomas AbbreviationsPLSCR1Phospholipid scramblase 1

CRCColorectal carcinomas

FBSFetal bovine serum

HLAHuman leukocyte antigen

ELISAEnzyme-linked immunosorbent assay

PBMCPeripheral blood mononuclear cell

RBCRed blood cell

pRbRetinoblastoma

SH3Src homology 3

VEGFVascular endothelial growth factor

PI3KPhosphoinositide 3 kinase

ADCCAntibody dependent cell-mediated cytotoxicity

NKNatural killer cell.

Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-10-254 contains supplementary material, which is available to authorized users.

Chung-Wei Fan, Chun-Yu Chen contributed equally to this work.

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Autor: Chung-Wei Fan - Chun-Yu Chen - Kuei-Tien Chen - Chia-Rui Shen - Yung-Bin Kuo - Ya-Shan Chen - Yeh-Pin Chou - Wei-Shan Wei

Fuente: https://link.springer.com/







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