The Role of Mast Cell Tryptase in Neoangiogenesis of Premalignant and Malignant Lesions of the Uterine Cervix

Benı́tez-Bribiesca, Luis; Wong, Alex K.; Utrera, Dolores; Castellanos, Emilio

doi:10.1177/002215540104900816

Cited by 113 publications

(75 citation statements)

References 8 publications

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“…In their study, Ranieri et al (36) reported that tryptase-positive mast cells positively correlated with angiogenesis in breast cancer. Further experimental evidence confirmed a correlation between angiogenesis and tryptasepositive mast cell counts in human endometrial (37) and invasive cervical cancers (38). Both parameters increased in accordance with tumor progression.…”

Section: Introductionsupporting

confidence: 54%

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

Goffredo

Gadaleta

Laterza

et al. 2013

Molecular and Clinical Oncology

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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.

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Section: Introductionsupporting

confidence: 54%

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

Goffredo

Gadaleta

Laterza

et al. 2013

Molecular and Clinical Oncology

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“…Tryptase-positive mast cells increase in number and vascularization increases in a linear fashion in solid tumors, such as human malignant melanoma , endometrial carcinoma (Benítez-Bribiesca et al 2001, Ribatti et al 2005, breast cancer (Ribatti et al, 2007a;Ranieri et al, 2009), uterine leiomyomas (Ribatti et al, 2007b), colorectal cancer (Gulubova and Vlaykova, 2009).…”

Section: Resultsmentioning

confidence: 99%

Tryptase and chymase are angiogenic in vivo in the chorioallantoic membrane assay

et al. 2011

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Human mast cells (MCs) are divided in two types depending on the expression of tryptase and chymase in their granules. Literature data indicate that both tryptase and chymase are angiogenic, but there is currently no evidence of their direct angiogenic activity in vivo. In this study, we have investigated the capacity of tryptase and chymase to promote vasoproliferation in chick embryo chorioallantoic membrane (CAM), a well established in vivo assay to study angiogenesis and anti-angiogenesis. The results showed that both tryptase and chymase stimulate angiogenesis and that the response is similar to that obtained with vascular endothelial growth factor (VEGF), a well-known angiogenic cytokine, and confirm the angiogenic activity of these two proteases stored in MC granules.

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“…For almost 20 years, in vitro and in vivo studies have linked mast cell (MC) degranulation and activation with angiogenesis and neovascularization (Folkman 1982, Levi Schaffer & Pe'er 2001, Norrby 2002). This assumption is partially supported by the close anatomical association between MCs and the vasculature, and the recruitment of these cells during tumour growth, wound healing and inflammation (Benítez-Bribiesca et al 2001, Fukushima et al 2001, Norrby 2002. Moreover, degranulation of MCs by a variety of secretagogues causes the release of potent angiogenic factors, e.g.…”

Section: Introductionmentioning

confidence: 99%

Mast cells degranulation affects angiogenesis in the rat uterine cervix during pregnancy

Varayoud¹,

Ramos²,

Bosquiazzo³

et al. 2004

Reproduction

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During pregnancy, it is essential that sufficient nutrients are supplied by the vascular system to support the dramatic modifications of the rat uterine cervix. Angiogenesis refers to the growth of new blood vessels from pre-existing microcirculation and mast cells have been associated with this process. This study examined the modifications of the vascular compartment and the distribution of mast cells on cervical tissue during pregnancy. Using disodium cromoglycate as a mast cell stabilizer, we determined the effects of the mast cell degranulation on cervical angiogenesis. Mast cell distribution and their degranulation status were evaluated by immunohistochemistry. Endothelial cell proliferation was measured by bromodeoxyuridine incorporation. Vascular areas (absolute and relative) and maturation indices were assessed by quantitative immunohistochemistry of von Willebrand factor and a-smooth muscle actin respectively. Mast cells were predominantly observed during the first half of pregnancy in the perivascular zones. The values of bromodeoxyuridine incorporation, absolute vascular area and vascular maturation index exhibited a significant increase throughout pregnancy. All animals that received mast cell stabilizer showed more than 40% of non-degranulated mast cells. Treated rats exhibited a decrease in endothelial proliferation and in relative vascular area; in addition, a large proportion of mature blood vessels was observed, suggesting a diminished level of new vessel formation. The effects of the mast cell stabilizer were sustained beyond the end of treatment. This is the first report that brings evidence that mast cell degranulation could be a necessary process to contribute to the normal angiogenesis of the rat cervix during pregnancy. Further investigations are needed to elucidate the possible implications of abnormal vascular development of the uterine cervix on the physiological process of ripening and parturition.

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The Role of Mast Cell Tryptase in Neoangiogenesis of Premalignant and Malignant Lesions of the Uterine Cervix

Cited by 113 publications

References 8 publications

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

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

Tryptase and chymase are angiogenic in vivo in the chorioallantoic membrane assay

Mast cells degranulation affects angiogenesis in the rat uterine cervix during pregnancy

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