Heparanase Expression in Circulating Lymphocytes of Breast Cancer Patients Depends on the Presence of the Primary Tumor and/or Systemic Metastasis

• Published in: Neoplasia (New York, N.Y.) Vol. 9; no. 6; pp. 504 - 510
• Main Authors: Theodoro, Thérése Rachell, de Matos, Leandro Luongo, Lambiasi Sant Anna, Aleksandra Vanessa, Fonseca, Fernando Luiz Affonso, Semedo, Patrícia, Martins, Lourdes Conceição, Nader, Helena Bonciani, Del Giglio, Auro, da Silva Pinhal, Maria Aparecida
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2007; Neoplasia Press Inc; Elsevier
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - immunology; Case-Control Studies; Female; Gene Expression Regulation, Enzymologic; Glucuronidase - genetics; Heparanase; Humans; Immunoenzyme Techniques; Lymphatic Metastasis - pathology; lymphocytes; Lymphocytes - enzymology; metastasis; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Tumor Cells, Cultured; tumor markers; Heparanase; breast cancer; lymphocytes; tumor markers; metastasis
• ISSN: 1476-5586; 1522-8002; 1476-5586; 1522-8002
• DOI: 10.1593/neo.07241

Heparanase is an endo-β-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.