title: Heparanase expression in circulating lymphocytes of breast cancer patients depends on the presence of the primary tumor and/or systemic metastasis.
abstract: Heparanase is an endo-beta-glucuronidase that is capable of degrading heparan sulfate chains of proteoglycans, generating a variety of bioactive molecules such as growth factors and chemotactic and angiogenic agents. The expression of heparanase was investigated in the peripheral blood mononuclear cell fraction (PBMC) of 30 patients with breast cancer and 20 healthy control women by reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry. PBMC samples from all breast cancer patients at study entry showed the expression of heparanase, whereas no expression was observed for healthy women. Immunocytochemistry analysis demonstrated that heparanase was expressed in lymphocytes of breast cancer PBMC. Throughout follow-up, heparanase expression by RTPCR decreased significantly after surgery in patients treated with neoadjuvant chemotherapy (P = .002) and after tamoxifen treatment (P = .040), whereas it increased significantly with the advent of systemic metastasis (P = .027). In vitro, either serum from breast cancer patients or a medium originated from coculture experiments of MCF-7 cells and lymphocytes from healthy women stimulated heparanase expression in normal lymphocytes. The results suggest that there is a tumor-inducing effect on heparanase expression by lymphocytes present in the PBMCs of breast cancer patients, which depends, in turn, on the interaction between a tumor and normal lymphocytes.
authors.affiliation: Departamento de Bioquímica, Faculdade de Medicina do ABC, São Paulo, Brazil.
authors.forename: Thérèse Rachell
authors.initials: TR
authors.lastname: Theodoro
authors.forename: Leandro Luongo
authors.initials: LL
authors.lastname: de Matos
authors.forename: Aleksandra Vanessa Lambiasi
authors.initials: AV
authors.lastname: Sant Anna
authors.forename: Fernando Luiz Affonso
authors.initials: FL
authors.lastname: Fonseca
authors.forename: Patrícia
authors.initials: P
authors.lastname: Semedo
authors.forename: Lourdes Conceição
authors.initials: LC
authors.lastname: Martins
authors.forename: Helena Bonciani
authors.initials: HB
authors.lastname: Nader
authors.forename: Auro
authors.initials: A
authors.lastname: Del Giglio
authors.forename: Maria Apareci
authors.initials: MA
authors.lastname: da Silva Pinhal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005966:Glucuronidase / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis / Q000473:pathology; D008214:Lymphocytes / Q000201:enzymology*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D012333:RNA, Messenger; D000099175:Heparanase