Heparanase expression in circulating lymphocytes of breast cancer patients depends on the presence of the primary tumor and/or systemic metastasis.
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.
Theodoro
Thérèse Rachell
TR
Departamento de Bioquímica, Faculdade de Medicina do ABC, São Paulo, Brazil.
de Matos
Leandro Luongo
LL
Sant Anna
Aleksandra Vanessa Lambiasi
AV
Fonseca
Fernando Luiz Affonso
FL
Semedo
Patrícia
P
Martins
Lourdes Conceição
LC
Nader
Helena Bonciani
HB
Del Giglio
Auro
A
da Silva Pinhal
Maria Apareci
MA
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
D005966:Glucuronidase; D012333:RNA, Messenger; D000099175:Heparanase