Crosstalk between tumor cells and lymphocytes modulates heparanase expression

Autor(es)

Theodoro, Therese Rachell ^[1] ; Matos, Leandro Luongo ^[2] ; Cavalheiro, Renan Pelluzzi ^[3] ; Justo, Giselle Zenker ^{[3, 4]} ; Nader, Helena Bonciani ^[3] ; Silva Pinhal, Maria Aparecida ^{[3, 1]}

Afiliação do(s) autor(es)

^[1] Fac Med ABC, Dept Biochem, Ave Lauro Gomes 2000, BR-09060870 Santo Andre, SP - Brazil

^[2] Univ Sao Paulo, Fac Med, Dept Surg, Head & Neck Discipline, Ave Dr Arnaldo 455, BR-01246903 Sao Paulo, SP - Brazil

^[3] Univ Fed Sao Paulo, Dept Biochem, Rua Tres Maio 100, BR-04044020 Sao Paulo, SP - Brazil

^[4] Univ Fed Sao Paulo, Dept Pharmaceut Sci, Rua Tres Maio 100, BR-04044020 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF TRANSLATIONAL MEDICINE; v. 17, MAR 29 2019.
• Citações Web of Science: 1

Resumo

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. (AU)

• Processo FAPESP: 16/01357-8 - Peptídeos ligantes de heparam sulfato, heparanase e HER2 com potencial efeito antitneoplásico
• Beneficiário: Maria Aparecida da Silva Pinhal
• Modalidade de apoio: Auxílio à Pesquisa - Regular