Tryptase serum levels in patients suffering from hepatocellular carcinoma undergoing intra-arterial chemoembolization: Possible predictive role of response to treatment

Abstract

Abstract. Tryptase is a serin protease stored in mast cell granules that has recently been found to be involved in tumor angiogenesis. Data from experimental tumor models have suggested that prior to the onset of angiogenesis mast cells were accumulated near tumor cells and were required for the macroscopic expansion and metastatic spread of primary tumor cells. Hepatocellular cancer (HCC) is a well-established, highly angiogenesis-dependent hypervascular tumor. The aim of this preliminary study was to assess tryptase serum levels in 30 HCC patients prior and subsequent to hepatic transarterial chemoembolization (TACE). In this study, patients with intermediate stage (B) HCC, according to the Barcelona Clinic Liver Cancer (BCLC) staging classification, were enrolled. Additional patient features were adequate liver functional reserve and A or B status, according to the Child-Pugh classification. Tryptase levels were measured using the UniCAP-Tryptase fluoroimmunoassay. TACE was performed by loading doxorubicin on microspheres. The mean ± standard deviation (SD) tryptase level pre-TACE was 7.74±3.62 µg/l, and post-TACE 4.67±2.79 µg/l. A statistically significant difference (P<0.001) was detected, using the Student's t-test, between pre-and post-TACE tryptase level concentrations. No correlations were found between tryptase levels and other important clinicopathological features of patients. This is the first preliminary study analyzing the potential significance of serum tryptase levels in HCC patients. The results demonstrated higher serum tryptase levels in HCC patients, suggesting tryptase release from HCC tissue. As expected, after TACE, serum tryptase levels were decreased. Therefore, we suggested that tryptase was a potential biomarker of response to TACE treatment in HCC patients.

Mast cell–induced immunopathology in recurrent pregnancy losses

“…They have an important role in angiogenesis through the direct proteolytic activity leading to degradation of extracellular matrix (ECM) and indirectly by activating MMPs and plasminogen activator, which are key enzymes of proteolytic systems that contribute to ECM degradation . Tryptases are secreted in active form (bound to heparan sulfate) and can act either directly on endothelial cells or indirectly on ECM to induce angiogenesis in tumors . Beside their role in angiogenesis, MCs play important role in inflammation and can transition from a protective immune cells to a potent pro‐inflammatory cells which have a significant impact on the progression of many autoimmune conditions, such as inflammatory bowel disease, insulin‐dependent diabetes mellitus, rheumatoid arthritis, psoriasis, multiple sclerosis, bullous pemphigoid, chronic idiopathic urticarial, systemic lupus erythematosus, and cutaneous vasculitis .…”

Mast Cell Targeted Chimeric Toxin Can Be Developed as an Adjunctive Therapy in Colon Cancer Treatment

“…The mechanisms that mast cells use in the tumorigenesis of cancer are not totally clear. The dual roles of mast cells in both promoting and inhibiting tumor growth have been widely reported [ 41 , 42 , 43 , 44 ]; a high level of mast cell infiltration has been found to indicate a poor prognosis in skin cancer [ 56 ], prostate cancer [ 41 ], oral squamous cell carcinoma [ 57 ], and several types of lymphomas [ 58 ] but, on the contrary, high mast cell numbers usually indicate a good prognostic outcome for several other cancers such as ovarian cancer, breast cancer, and non-small cell lung cancer [ 59 ]. Summarizing recent research, mast cells can promote tumorigenesis in the following ways: promoting the proliferation of tumor cells by the secretion of growth factors; facilitating tumor cell detachment from the matrix and migration by secreting protease; providing angiogenic cytokines for angiogenesis in the local environment that leads to tumor progression.…”

“…Immunohistochemistry studies to quantify the number of mast cells in tumors were conducted on the patient specimens using antibodies against c-kit and tryptase (Abcam, Cambridge, MA, USA), which are specifically expressed in mast cells [ 43 , 44 ]. 4 µm sections of the human colon tissues were treated for antigen retrieval for one hour in a steamer containing 10 mmol/L citrate buffer (pH 6.0).…”

“…MC tryptase can be detected in the peripheral blood of pancreatic cancer patients [ 42 ]. In hepatocellular carcinoma, higher peritumoral MC density was associated with poorer clinical outcomes and an increased probability of early recurrence [ 43 ]. As a specific marker of mast cells, c-kit expression has been found to be a poor prognostic indicator in phyllodes tumors of the breast [ 44 ].…”

Mast cells positive to tryptase, endothelial cells positive to protease-activated receptor-2, and microvascular density correlate among themselves in hepatocellular carcinoma patients who have undergone surgery

“…In literature, no data have been published on the relationship between MC density positive to tryptase (MCDPT), ECs positive to PAR-2 forming microvascular density (PAR-2-MVD), and classical MVD (C-MVD) in hepatocellular carcinoma (HCC) angiogenesis. 28 – 30 …”