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.

Analysis of heparanase isoforms and cathepsin B in the plasma of patients with gastrointestinal carcinomas: analytical cross-sectional study

“…[28][29][30] It had already been observed in previous studies from our laboratory that heparanase-1 and heparanase-2 isoforms were overexpressed in the blood (mononuclear cell fraction) of women with breast cancer, thereby suggesting that this tumor can possibly modulate the expression of both heparanases. 31 Similar results have been described, suggesting that higher heparanase expression in gastric cancer tissues was closely correlated with lower treatment responsiveness and poor prognosis. 32 The data obtained in the present study demonstrated that heparanase-2 protein expression was significantly greater in plasma samples from patients with gastrointestinal carcinomas, compared with healthy individuals.…”

Heparanase-2, syndecan-1, and extracellular matrix remodeling in colorectal carcinoma

“…Despite the fact that both HPA1 and HPA2 are encoded by different genes, some data obtained in our laboratory had demonstrated that serum or plasma from cancer patients or tumor cells can stimulate expression of both heparanases in peripheral blood healthy lymphocytes [59], suggesting that these proteins may present at least one mechanism of gene control in common.…”

Las Células TC-1 Implantadas Invaden a las Fibras Musculares Esqueléticas Adyacentes en un Modelo Murino de Cáncer

“…Estos resultados sugieren que las células TC-1 sintetizan y secretan componentes de la matriz extracelular, lo que favorece su migración e invasión a tejidos distantes a su sitio de implante. Este mecanismo ha sido descrito en tipos celulares como carcinoma pulmonar humano (Bolon et al, 1995;Kikkawa et al, 1998) y cáncer de mama (Yee et al, 2007;Theodoro et al, 2007). En la literatura no encontramos reportes que describan este fenómeno para las células TC-1.…”