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

Goffredo,Veronica; Gadaleta,Cosmo Damiano; Laterza,Annamaria; Vacca,Angelo; Ranieri,Girolamo

doi:10.3892/mco.2013.59

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

Authors:
- Veronica Goffredo
- Cosmo Damiano Gadaleta
- Annamaria Laterza
- Angelo Vacca
- Girolamo Ranieri
View Affiliations

Affiliations: Interventional Radiology and Medical Oncology Unit, National Cancer Research Centre, Cancer Institute ‘Giovanni Paolo II’, Bari, Italy, Laboratory of Analyses, Department of Experimental Oncology, National Cancer Research Centre, Cancer Institute ‘Giovanni Paolo II’, Bari, Italy, Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy
Published online on: January 3, 2013 https://doi.org/10.3892/mco.2013.59
Pages: 385-389

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

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.

View Figures

View References

1	Hallgren J and Pejler G: Biology of mast cell tryptase: an inflammatory mediator. FEBS J. 25:234–241. 2006.
2	Schwartz LB, Yunginger JW, Miller J, Bokhari R and Dull D: Time course of appearance and disappearance of human mast cell tryptase in the circulation after anaphylaxis. J Clin Invest. 83:1551–1555. 1989. View Article : Google Scholar : PubMed/NCBI
3	Metz M, Grimbaldeston MA, Nakae S, Piliponsky AM, Tsai M and Galli SJ: Mast cells in the promotion and limitation of chronic inflammation. Immunol Rev. 17:304–328. 2007. View Article : Google Scholar
4	Ackermann MR: Acute inflammation. Pathologic Basis of Veterinary Disease. McGavin MD and Zachary JF: Mosby Elsevier; Philadelphia: pp. 117–118. 2007
5	Ackermann MR: Chronic inflammation and wound healing. Pathologic Basis of Veterinary Disease. McGavin MD and Zachary JF: Mosby Elsevier; Philadelphia: pp. 1742007
6	Kovanen PT: Mast cells: multipotent local effector cells in atherothrombosis. Immunol Rev. 217:105–122. 2007. View Article : Google Scholar : PubMed/NCBI
7	Theoharides TC and Conti P: Mast cells: the Jekyll and Hyde of tumor growth. Trends Immunol. 25:235–241. 2004. View Article : Google Scholar : PubMed/NCBI
8	Zizzo N, Patruno R, Zito FA, Di Summa A, Tinelli A, Troilo S, Misino A, Ruggieri E, Goffredo V, Gadaleta CD and Ranieri G: Vascular endothelial growth factor concentrations from platelets correlate with tumor angiogenesis and grading in a spontaneous canine non-Hodgkin lymphoma model. Leuk Lymphoma. 51:291–296. 2010. View Article : Google Scholar
9	Ribatti D and Vacca A: Overview of angiogenesis during tumor growth. Angiogenesis: An Integrative Approach from Science to Medicine. Figg WD and Folkman J: Springer-Verlag; Berlin: pp. 161–168. 2008, View Article : Google Scholar
10	Nielsen HJ, Hanse U, Christensen IJ, Reimert CM, Brunner N and Moesgaard F: Independent prognostic value of eosinophil and mast cell infiltration in colorectal cancer tissue. J Pathol. 189:487–495. 1999. View Article : Google Scholar : PubMed/NCBI
11	Bowrey PF, King J, Magarey C, Schwartz P, Marr P, Bolton E and Morris DL: Histamine, mast cells and tumour cell proliferation in breast cancer: does preoperative cimetidine administration have an effect? Br J Cancer. 82:167–170. 2000. View Article : Google Scholar : PubMed/NCBI
12	Erol YA and Ozdemir O: Mast cells: Are they really related to invasiveness of endometrial carcinoma? Pathol Res Pract. 206:426–428. 2010. View Article : Google Scholar : PubMed/NCBI
13	Graham RM and Graham JB: Mast cells and cancer of the cervix. Surg Gynecol Obstet. 123:3–9. 1996.
14	Tan ST, Wallis RA, He Y and Davis PF: Mast cells and hemangioma. Plast Reconstr Surg. 113:999–1011. 2004. View Article : Google Scholar : PubMed/NCBI
15	Ribatti D, Vacca A, Nico B, Quondamatteo F, Ria R, Minischetti M, Marzullo A, Herken R, Roncali L and Dammacco F: Bone marrow angiogenesis and mast cell density increase simultaneously with progression of human multiple myeloma. Br J Cancer. 79:451–455. 1999. View Article : Google Scholar : PubMed/NCBI
16	Blair RJ, Meng H, Marchese MJ, Ren S, Schwartz LB, Tonnesen MG and Gruber BL: Tryptase is a novel, potent angiogenic factor. J Clin Invest. 99:2691–2700. 1997. View Article : Google Scholar : PubMed/NCBI
17	Ribatti D, Ranieri G, Nico B, Benagiano V and Crivellato E: Tryptase and chymase are angiogenic in vivo in the chorioallantoic membrane assay. Int J Dev Biol. 55:99–102. 2011. View Article : Google Scholar : PubMed/NCBI
18	Ruoss SJ, Hartmann T and Caughey GH: Mast cell tryptase is a mitogen for cultured fibroblasts. J Clin Invest. 88:493–499. 1991. View Article : Google Scholar : PubMed/NCBI
19	Hartmann T, Ruoss SJ, Raymond WW, Seuwen K and Caughey GH: Human tryptase as a potent, cell-specific mitogen: role of signaling pathways in synergistic responses. Am J Physiol. 262:528–534. 1992.PubMed/NCBI
20	Abe M, Kurosawa M, Ishikawa O, Miyachi Y and Kido H: Mast cell tryptase stimulates both human dermal fibroblast proliferation and type I collagen production. Clin Exp Allergy. 28:1509–1517. 1998. View Article : Google Scholar : PubMed/NCBI
21	Frungieri MB, Albrecht M, Raemsch R and Mayerhofer A: The action of the mast cell product tryptase on cyclooxygenase-2 (COX2) and subsequent fibroblast proliferation involves activation of the extracellular signal-regulated kinase isoforms 1 and 2 (erk1/2). Cell Signal. 17:525–533. 2005. View Article : Google Scholar
22	Briggaman RA, Schechter NM, Fräki JE and Lazarus GS: Degradation of the epidermal-dermal junction by proteolytic enzymes from human skin and human polymorphonuclear leukocytes. J Exp Med. 160:1027–1042. 1984. View Article : Google Scholar : PubMed/NCBI
23	Kaminska R, Helisalmi P, Harvima RJ, Naukkarinen A, Horsmanheimo M and Harvima IT: Focal dermal-epidermal separation and fibronectin cleavage in basement membrane by human mast cell tryptase. J Invest Dermatol. 113:567–573. 1999. View Article : Google Scholar : PubMed/NCBI
24	Huttunen M and Harvima IT: Mast cell tryptase and chymase in chronic leg ulcers: chymase is potentially destructive to epithelium and is controlled by protease inhibitors. Br J Dermatol. 152:1149–1160. 2005. View Article : Google Scholar : PubMed/NCBI
25	Lohi J, Harvima I and Keski-Oja J: Pericellular substrates of human mast cell tryptase: 72 000 dalton gelatinase and fibronectin. J Cell Biochem. 50:337–349. 1992. View Article : Google Scholar : PubMed/NCBI
26	Saarinen J, Kalkkinen N, Welgus HG and Kovanen PT: Activation of human interstitial procollagenase through direct cleavage of the Leu83-Thr84 bond by mast cell chymase. J Biol Chem. 269:18134–18140. 1994.PubMed/NCBI
27	Gruber BL, Marchese MJ, Suzuki K, Schwartz LB, Okada Y, Nagase H and Ramamurthy NS: Synovial procollagenase activation by human mast cell tryptase: dependence upon matrix metalloproteinase 3 activation. J Clin Invest. 84:1657–1662. 1989. View Article : Google Scholar : PubMed/NCBI
28	Stack MS and Johnson DA: Human mast cell tryptase activates single-chain urinary-type plasminogen activator (pro-urokinase). J Biol Chem. 269:9416–9419. 1994.PubMed/NCBI
29	Kemik O, Sumer A, Kemik SA, Purisa S and Tuzun S: Circulating levels of VEGF family and their receptors in hepatocellular carcinoma. Bratisl Lek Listy. 111:485–488. 2010.PubMed/NCBI
30	Shimanuki Y, Takahashi K, Cui R, Hori S, Takahashi F, Miyamoto H and Fukurchi Y: Role of serum vascular endothelial growth factor in the prediction of angiogenesis and prognosis for non-small cell lung cancer. Lung. 183:29–42. 2005. View Article : Google Scholar : PubMed/NCBI
31	Carvalho RF, Nilsson G and Harvima IT: Increased mast cell expression of PAR-2 in skin inflammatory diseases and release of IL-8 upon PAR-2 activation. Exp Dermatol. 19:117–122. 2010. View Article : Google Scholar : PubMed/NCBI
32	Ribatti D, Nico B, Vacca A, Marzullo A, Calvi N, Roncali L and Dammacco F: Do mast cells help to induce angiogenesis in B-cell non-Hodgkin’s lymphomas? Br J Cancer. 77:1900–1906. 1998.PubMed/NCBI
33	Ribatti D, Polimeno G, Vacca A, Marzullo A, Crivellato E, Nico B, Lucarelli G and Dammacco F: Correlation of bone marrow angiogenesis and mast cells with tryptase activity in myelodysplastic syndromes. Leukemia. 16:1680–1684. 2002. View Article : Google Scholar : PubMed/NCBI
34	Ribatti D, Molica S, Vacca A, Nico B, Crivellato E, Roccaro AM and Dammacco F: Tryptase-positive mast cells correlate positively with bone marrow angiogenesis in B-cell chronic lymphocytic leukemia. Leukemia. 17:1428–1430. 2003. View Article : Google Scholar : PubMed/NCBI
35	Molica S, Vacca A, Crivellato E, Cuneo A and Ribatti D: Tryptase-positive mast cells predict clinical outcome of patients with early B-cell chronic lymphocytic leukemia. Eur J Haematol. 71:137–139. 2003. View Article : Google Scholar : PubMed/NCBI
36	Ranieri G, Ammendola M, Patruno R, Celano G, Zito FA, Montemurro S, Rella A, Di Lecce V, Gadaleta CD, Battista De Sarro G and Ribatti D: Tryptase-positive mast cells correlate with angiogenesis in early breast cancer patients. Int J Oncol. 35:115–120. 2009. View Article : Google Scholar : PubMed/NCBI
37	Ribatti D, Finato N, Crivellato E, Marzullo A, Mangieri D, Nico B, Vacca A and Beltrami CA: Neovascularization and mast cells with tryptase activity increase simultaneously with pathologic progression in human endometrial cancer. Am J Obstet Gynecol. 193:1961–1965. 2005. View Article : Google Scholar : PubMed/NCBI
38	Benítez-Bribiesca L, Wong A, Utrera D and Castellanos E: The role of mast cell tryptase in neoangiogenesis of premalignant and malignant lesions of the uterine cervix. J Histochem Cytochem. 49:1061–1062. 2001.PubMed/NCBI
39	Cervello M, Foderàa D, Florena AM, Soresi M, Tripodo C, D’Alessandro N and Montalto G: Correlation between expression of cyclooxygenase-2 and the presence of inflammatory cells in human primary hepatocellular carcinoma: possible role in tumor promotion and angiogenesis. World J Gastroenterol. 11:4638–4644. 2005.
40	Ranieri G, Gadaleta-Caldarola G, Goffredo V, Patruno R, Mangia A, Rizzo A, Sciorsci RL and Gadaleta CD: Sorafenib (BAY 43-9006) in hepatocellular carcinoma patients: from discovery to clinical development. Curr Med Chem. 19:938–944. 2012. View Article : Google Scholar : PubMed/NCBI
41	Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX, Sherman M, Schwartz M, Lotze M, Talwalkar J and Gores GJ: Panel of Experts in HCC-Design Clinical Trials: Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst. 100:698–711. 2008. View Article : Google Scholar