LRP-1 Matricellular Receptor Involvement in Triple Negative Breast Cancer Tumor Angiogenesis

被引：12

作者：

Campion, Oceane ^{[1
,2
]}

Devy, Jessica Thevenard ^{[1
,2
]}

Billottet, Clotilde ^{[3
]}

Schneider, Christophe ^{[1
,2
]}

Etique, Nicolas ^{[1
,2
]}

Dupuy, Jean-William ^{[4
]}

Raymond, Anne-Aurelie ^{[5
]}

Rombi, Camille Boulagnon ^{[2
,6
]}

Meunier, Marie ^{[1
,2
]}

Djermoune, El-Hadi ^{[7
]}

Lelievre, Elodie ^{[1
,2
]}

Wahart, Amandine ^{[1
,2
]}

Bour, Camille ^{[1
,2
]}

Hachet, Cathy ^{[1
,2
]}

Cairo, Stefano ^{[8
]}

Bikfalvi, Andreas ^{[3
]}

Dedieu, Stephane ^{[1
,2
]}

Devy, Jerome ^{[1
,2
]}

机构：

[1] Univ Reims, UFR Sci Exactes & Nat, F-51687 Reims, France

[2] CNRS, UMR 7369, MEDyC, Matrice Extracellulaire & Dynam Cellulaire, F-51687 Reims, France

[3] Univ Bordeaux, U1029, LAMC, INSERM, F-33600 Pessac, France

[4] Univ Bordeaux, Plateforme Proteome, F-33076 Bordeaux, France

[5] TBM Core US 005, Plateforme Oncoprot, F-33000 Bordeaux, France

[6] CHU Reims, Lab Anat Pathol, F-51100 Reims, France

[7] Univ Lorraine, CRAN, CNRS, F-54000 Nancy, France

[8] Xentech, F-91000 Evry, France

来源：

BIOMEDICINES | 2021年 / 9卷 / 10期

关键词：

breast cancer; TNBC; LRP-1; angiogenesis; CELL-PROLIFERATION; ENDOTHELIAL-CELLS; LDL RECEPTOR; PROTEIN-1; METASTASIS; THROMBOSPONDIN-1; EXPRESSION; CHALLENGES; STABILITY; MODULATOR;

D O I：

10.3390/biomedicines9101430

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Background: LRP-1 is a multifunctional scavenger receptor belonging to the LDLR family. Due to its capacity to control pericellular levels of various growth factors and proteases, LRP-1 plays a crucial role in membrane proteome dynamics, which appears decisive for tumor progression. Methods: LRP-1 involvement in a TNBC model was assessed using an RNA interference strategy in MDA-MB-231 cells. In vivo, tumorigenic and angiogenic effects of LRP-1-repressed cells were evaluated using an orthotopic xenograft model and two angiogenic assays (Matrigel(R) plugs, CAM). DCE-MRI, FMT, and IHC were used to complete a tumor longitudinal follow-up and obtain morphological and functional vascular information. In vitro, HUVECs' angiogenic potential was evaluated using a tumor secretome, subjected to a proteomic analysis to highlight LRP-1-dependant signaling pathways. Results: LRP-1 repression in MDA-MB-231 tumors led to a 60% growth delay because of, inter alia, morphological and functional vascular differences, confirmed by angiogenic models. In vitro, the LRP-1-repressed cells secretome restrained HUVECs' angiogenic capabilities. A proteomics analysis revealed that LRP-1 supports tumor growth and angiogenesis by regulating TGF-beta signaling and plasminogen/plasmin system. Conclusions: LRP-1, by its wide spectrum of interactions, emerges as an important matricellular player in the control of cancer-signaling events such as angiogenesis, by supporting tumor vascular morphology and functionality.

引用

页数：22

共 66 条

[1] Thrombospondin-1 and transforming growth factor-beta1 promote breast tumor cell invasion through upregulation of the plasminogen/plasmin system [J].