Please use this identifier to cite or link to this item: https://observatorio.fm.usp.br/handle/OPI/31866
Title: Crosstalk between tumor cells and lymphocytes modulates heparanase expression
Authors: THEODORO, Therese RachellMATOS, Leandro LuongoCAVALHEIRO, Renan PelluzziJUSTO, Giselle ZenkerNADER, Helena BoncianiPINHAL, Maria Aparecida Silva
Citation: JOURNAL OF TRANSLATIONAL MEDICINE, v.17, article ID 103, 14p, 2019
Abstract: BackgroundHeparanase (HPSE) is an endo-beta-glucuronidase that degrades heparan sulfate (HS) chains on proteoglycans. The oligosaccharides generated by HPSE promote angiogenesis, tumor growth and metastasis. Heparanase-2 (HPSE2), a close homolog of HPSE, does not exhibit catalytic activity. Previous studies have demonstrated that serum or plasma from breast cancer patients showed increased expression of both heparanases in circulating lymphocytes. The aim of this study was to better understand the mechanisms involved in the upregulation of heparanases in circulating lymphocytes.MethodsLymphocytes collected from healthy women were incubated in the presence of MCF-7 breast cancer cells (co-culture) to stimulate HPSE and HPSE2 overexpression. The protein level of heparanases was evaluated by immunocytochemistry, while mRNA expression was determined by quantitative RT-PCR.ResultsThe medium obtained from co-culture of MCF-7 cells and circulating lymphocytes stimulated the expression of HPSE and HPSE2. Previous treatment of the co-culture medium with an anti-heparan sulfate proteoglycan antibody or heparitinase II inhibited the upregulation of heparanases in circulating lymphocytes. The addition of exogenous heparan sulfate (HS) enhanced the expression of both heparanases. Moreover, the co-cultured cells, as well as MCF-7 cells, secreted a higher number of exosomes expressing an increased level of HS compared to that of the exosomes secreted by circulating lymphocytes from women who were not affected by cancer.ConclusionsThe results revealed that HS is likely responsible for mediating the expression of heparanases in circulating lymphocytes. HS secreted by tumor cells might be carried by exosome particles, confirming the key role of tumor cells, as well as secreted HS, in upregulating the expression of heparanases, suggesting a possible mechanism of crosstalk between tumor cells and circulating lymphocytes.
Appears in Collections:Artigos e Materiais de Revistas Científicas - HC/ICESP
Artigos e Materiais de Revistas Científicas - LIM/28

Files in This Item:
File Description SizeFormat 
art_THEODORO_Crosstalk_between_tumor_cells_and_lymphocytes_modulates_heparanase_2019.PDFpublishedVersion (English)1.65 MBAdobe PDFThumbnail
View/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.