scholarly journals A Pro-Tumorigenic Effect of Heparanase 2 (Hpa2) in Thyroid Carcinoma Involves Its Localization to the Nuclear Membrane

2021 ◽  
Vol 11 ◽  
Author(s):  
Itai Margulis ◽  
Inna Naroditsky ◽  
Miriam Gross-Cohen ◽  
Neta Ilan ◽  
Israel Vlodavsky ◽  
...  

Activity of the endo-beta-glucuronidase heparanase, capable of cleaving heparan sulfate (HS), is most often elevated in many types of tumors, associating with increased tumor metastasis and decreased patients’ survival. Heparanase is therefore considered to be a valid drug target, and heparanase inhibitors are being evaluated clinically in cancer patients. Heparanase 2 (Hpa2) is a close homolog of heparanase that gained very little attention, likely because it lacks HS-degrading activity typical of heparanase. The role of Hpa2 in cancer was not examined in detail. In head and neck cancer, high levels of Hpa2 are associated with decreased tumor cell dissemination to regional lymph nodes and prolonged patients’ survival, suggesting that Hpa2 functions to attenuate tumor growth. Here, we examined the role of Hpa2 in normal thyroid tissue and in benign thyroid tumor, non-metastatic, and metastatic papillary thyroid carcinoma (PTC) utilizing immunostaining in correlation with clinicopathological parameters. Interestingly, we found that Hpa2 staining intensity does not significantly change in the transition from normal thyroid gland to benign, non-metastatic, or metastatic thyroid carcinoma. Remarkably, we observed that in some biopsies, Hpa2 is accumulating on the membrane (envelop) of the nucleus and termed this cellular localization NM (nuclear membrane). Notably, NM localization of Hpa2 occurred primarily in metastatic PTC and was associated with an increased number of positive (metastatic) lymph nodes collected at surgery. These results describe for the first time unrecognized localization of Hpa2 to the nuclear membrane, implying that in PTC, Hpa2 functions to promote tumor metastasis.

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Raquel Weber ◽  
Ana Paula Santin Bertoni ◽  
Laura Walter Bessestil ◽  
Ilma Simoni Brum ◽  
Tania Weber Furlanetto

Goiter is more common in women, suggesting that estrogen could be involved in its physiopathology. The presence of classical estrogen receptors (ERαand ERβ) has been described in thyroid tissue, suggesting a direct effect of estrogen on the gland. A nonclassic estrogen receptor, the G-protein-coupled estrogen receptor (GPER1), has been described recently in several tissues. However, in goiter, the presence of this receptor has not been studied yet. We investigated GPER1 gene and protein expressions in normal thyroid and goiter using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot, respectively. In normal thyroid (n=16) and goiter (n=19), GPER1 gene was expressed in all samples, while GPER1 protein was expressed in all samples of normal thyroid (n=15) but in only 72% of goiter samples (n=13). When comparing GPER1 gene and protein levels in both conditions, gene expression and protein levels were higher in normal thyroid than in goiter, suggesting a role of this receptor in this condition. Further studies are needed to elucidate the role of GPER1 in normal thyroid and goiter.


1997 ◽  
Vol 44 (5) ◽  
pp. 697-700 ◽  
Author(s):  
MAKOTO KOMATSU ◽  
NOBUO ITOH ◽  
MASANOBU YAZAWA ◽  
SHINYA KOBAYASHI ◽  
KAZUAKI INOUE ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-2
Author(s):  
Angela Orcurto ◽  
Benoît Lhermitte ◽  
Alain Sermier ◽  
Dominik Berthold

Kidney lesions may be difficult to diagnose only by radiological exams, often requiring proof by tissue biopsy. Moreover, if enlarged regional lymph nodes are also present, the spectrum of differential diagnoses is even greater. The role of regional lymph node dissection in this setting is not clearly established. We show the case of a patient with a kidney mass associated with a conglomerate of para-aortic and iliac lymphadenopathies corresponding to an oncocytoma and a nodular lymphocyte predominant Hodgkin' lymphoma, respectively. Diagnosis of these two lesions was performed by morphology and immunohistochemistry. This case reflects how imaging can mislead to diagnosis and how histological confirmation helps decide treatment management.


1967 ◽  
Vol 53 (2) ◽  
pp. 141-148 ◽  
Author(s):  
Natale Cascinelli ◽  
Cesare Bartoli ◽  
Maurizio Turm

From 1928 to 1965, 383 cases of thyroid carcinoma were studied at the National Cancer Institute of Milan; among these cases 113 had distant metastases. The metastases were more frequent in patients aged fro 60 to 69. The female/male ratio was about 2:1. The lesions were more often in the skeleton (74 cases) and in the lungs (64 cases). Since a high incidence of skeletal metastases without lung involvement has been observed, the authors postulate that metastatic spread from thyroid carcinoma may occur also through vertebral veins. In undifferentiated carcinomas distant metastases occur quite early (87 % at 5 years). On the contrary, in differentiated carcinomas, metastases occur later: after 5 years from thyroidectomy in 31 per cent of patients with follicular carcinomas metastases were found and in 74 per cent after 10 years. In papillary carcinomas the percentage is 17 and 52 after 5 and 10 years respectively. Among 113 cases with distant metastases, 50 showed the first metastatic localization to the regional lymph nodes; this occurrence was found to be more frequent in papillary and unidifferentiated carcinomas (χ2 = 11.805).


2000 ◽  
Vol 68 (11) ◽  
pp. 6355-6361 ◽  
Author(s):  
Maria Valdrinez Campana Lonardoni ◽  
Momtchillo Russo ◽  
Sonia Jancar

ABSTRACT In the present study we investigated the role of platelet-activating factor (PAF) and prostaglandins in experimental Leishmania (Leishmania)amazonensis infection and the relationship between these mediators and nitric oxide (NO) production. Mouse peritoneal macrophages elicited with thioglicolate were infected with leishmania amastigotes, and the infection index determined 48 h later. The course of infection was monitored for 5 weeks in mice infected in the footpad with promastigotes by measuring the footpad swelling and parasite load in regional lymph nodes and spleen. The addition of PAF to C57BL/6 mouse macrophages significantly inhibited parasite growth and induced NO production. Treatment of macrophages with a selective PAF antagonist, WEB2086, increased the infection, indicating that endogenously produced PAF regulates macrophage ability to control leishmania infection. This effect of PAF was abolished by addition of the inhibitor of NO synthesis, L-NAME, to the cultures. The addition of prostaglandin E2 significantly increased the infection and NO production. Treatment with cyclo-oxygenase inhibitor, indomethacin, reduced the infection and PAF-induced release of NO. Thus, the increased NO production induced by PAF seems to be mediated by prostaglandins. The more-selective inhibitors of cyclo-oxygenase 2, nimesulide and NS-398, had no significant effect. Thus, antileishmanial activity correlates better with the presence of PAF or absence of prostaglandins than with NO production. In vivo treatment with PAF antagonists significantly increased leishmania lesions, as well as the parasite load, in regional lymph nodes and spleens. These findings indicate that PAF is essential for the control of leishmania infection.


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