Tumor- and host-derived heparanase-2 (Hpa2) attenuates tumorigenicity: role of Hpa2 in macrophage polarization and BRD7 nuclear localization.

Little attention was given to heparanase 2 (Hpa2) over the last two decades, possibly because it lacks a heparan sulfate (HS)-degrading activity typical of heparanase. Emerging results suggest, nonetheless, that Hpa2 plays a role in human pathologies, including cancer progression where it functions as a tumor suppressor. Here, we examined the role of Hpa2 in cervical carcinoma.

Nuclear localization of heparanase 2 (Hpa2) attenuates breast carcinoma growth and metastasis.

Unlike the intense research effort devoted to exploring the significance of heparanase in cancer, very little attention was given to Hpa2, a close homolog of heparanase. Here, we explored the role of Hpa2 in breast cancer. Unexpectedly, we found that patients endowed with high levels of Hpa2 exhibited a higher incidence of tumor metastasis and survived less than patients with low levels of Hpa2.

Lytic Mastoid Lesion in a Patient with Otalgia.

The differential diagnosis for an isolated lytic mastoid lesion is broad, encompassing various conditions requiring careful consideration. These include granulomatous disorders such as Langerhans cell histiocytosis and sarcoidosis, neoplastic processes like multiple myeloma, leukemia, lymphoma, and metastases, primary bone diseases such as Paget's disease, fibrous dysplasia, and osteitis fibrosa cystica, as well as infectious causes like osteomyelitis. In this report, we present a patient with otalgia and an isolated lytic mastoid lesion.

Heparanase 2 (Hpa2)- a new player essential for pancreatic acinar cell differentiation.

Heparanase 2 (Hpa2, HPSE2) is a close homolog of heparanase. Hpa2, however, lacks intrinsic heparan sulfate (HS)-degrading activity, the hallmark of heparanase enzymatic activity. Mutations of HPSE2 were identified in patients diagnosed with urofacial syndrome (UFS), a rare genetic disorder that exhibits abnormal facial expression and bladder voiding dysfunction, leading to renal damage and eventually renal failure.

Primary high-grade myoepithelial carcinoma of the lung: A study of three cases illustrating frequent SMARCB1-deficiency and review of the literature.

Primary myoepithelial carcinoma of the lung is exceptionally rare and, hence, remained poorly characterized. We present 3 tumors affecting 2 males and 1 female aged 60 to 84 years. Tumor size ranged from 4 to 10 cm.

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

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.

Heparanase 2 (Hpa2) attenuates the growth of pancreatic carcinoma.

While the pro-tumorigenic properties of the ECM-degrading heparanase enzyme are well documented, the role of its close homolog, heparanase 2 (Hpa2), in cancer is largely unknown. We examined the role of Hpa2 in pancreatic cancer, a malignancy characterized by a dense fibrotic ECM associated with poor response to treatment and bad prognosis. We show that pancreatic ductal adenocarcinoma (PDAC) patients that exhibit high levels of Hpa2 survive longer than patients with low levels of Hpa2.

Primary synovial sarcoma of the mediastinum: a rare tumor diagnosed by endoscopic ultrasound-fine needle biopsy (EUS-FNB)-Cytomorphologic, immunohistochemical, and molecular analysis.

Primary synovial sarcoma is exceedingly rare in the mediastinum. The differential diagnosis of this rare tumor is complex as a wide array of primary and metastatic tumors occur in this site.A definite diagnosis might be challenging even after tissue sampling.

Prognostic significance of heparanase expression in primary and metastatic breast carcinoma.

High levels of heparanase are detected in many types of tumors, associated with bad prognosis. Typically, heparanase levels are evaluated in a biopsy taken from the primary lesion, whereas its expression by the resulting metastases is most often unresolved. This becomes critically important as anti-heparanase compounds enter advanced clinical trials.

Targeting heparanase to the mammary epithelium enhances mammary gland development and promotes tumor growth and metastasis.

Heparanase is an endoglucuronidase that uniquely cleaves the heparan sulfate side chains of heparan sulfate proteoglycans. This activity ultimately alters the structural integrity of the ECM and basement membrane that becomes more prone to cellular invasion by metastatic cancer cells and cells of the immune system. In addition, enzymatically inactive heparanase was found to facilitate the proliferation and survival of cancer cells by activation of signaling molecules such as Akt, Src, signal transducer and activation of transcription (Stat), and epidermal growth factor receptor.

Pyogenic Granuloma: Possible Cause for Macroscopic Hematuria in Children.

Pyogenic granuloma (PG) is a benign, vascular tumor that is rarely reported in the urinary tract of pediatric population. Herein we present a case of a child followed up for recurrent painless macroscopic hematuria. We performed ureteroscopy, and a whitish lesion was discovered in the upper calyx of the right kidney.

The prognostic significance of heparanase expression in metastatic melanoma.

Background: Heparanase expression is induced in many types of cancers, including melanoma, and promotes tumor growth, angiogenesis and metastasis. However, there is insufficient data regarding heparanase expression in the metastatic lesions that are the prime target for anti-cancer therapeutics. To that end, we examined heparanase expression in metastatic melanoma and its correlation with clinical parameters.

Heparanase 2 Attenuates Head and Neck Tumor Vascularity and Growth.

The endoglycosidase heparanase specifically cleaves the heparan sulfate (HS) side chains on proteoglycans, an activity that has been implicated strongly in tumor metastasis and angiogenesis. Heparanase-2 (Hpa2) is a close homolog of heparanase that lacks intrinsic HS-degrading activity but retains the capacity to bind HS with high affinity. In head and neck cancer patients, Hpa2 expression was markedly elevated, correlating with prolonged time to disease recurrence and inversely correlating with tumor cell dissemination to regional lymph nodes, suggesting that Hpa2 functions as a tumor suppressor.

Heparanase 2 expression inversely correlates with bladder carcinoma grade and stage.

While the pro-tumorigenic function of heparanase is well taken, the role of its close homolog, heparanase 2 (Hpa2) in cancer is by far less investigated. Utilizing immunohistochemical analysis we found that Hpa2 is expressed by normal bladder transitional epithelium and its levels are decreased substantially in bladder cancer. Notably, tumors that retain high levels of Hpa2 were diagnosed as low grade (p=0.

Heparanase-neutralizing antibodies attenuate lymphoma tumor growth and metastasis.

Heparanase is an endoglycosidase that cleaves heparan sulfate side chains of proteoglycans, resulting in disassembly of the extracellular matrix underlying endothelial and epithelial cells and associating with enhanced cell invasion and metastasis. Heparanase expression is induced in carcinomas and sarcomas, often associating with enhanced tumor metastasis and poor prognosis. In contrast, the function of heparanase in hematological malignancies (except myeloma) was not investigated in depth.

Heparanase Enhances Tumor Growth and Chemoresistance by Promoting Autophagy.

Heparanase is the only enzyme in mammals capable of cleaving heparan sulfate, an activity implicated in tumor inflammation, angiogenesis, and metastasis. Heparanase is secreted as a latent enzyme that is internalized and subjected to proteolytic processing and activation in lysosomes. Its role under normal conditions has yet to be understood.

Involvement of Heparanase in Empyema: Implication for Novel Therapeutic Approaches.

Pleural empyema is an inflammatory condition that progresses from acute to chronic, life-threatening, phase. The incidence of empyema has been increasing both in children and adults worldwide in the past decades, mainly in healthy young adults and in older patients. Despite continued advances in the management of this condition, morbidity and mortality have essentially remained static over the past decade.

Pazopanib for metastatic pulmonary epithelioid hemangioendothelioma-a suitable treatment option: case report and review of anti-angiogenic treatment options.

Background: Epithelioid hemangioendothelioma is a rare vascular tumor of borderline or low-grade malignancy. The lungs and liver are the two common primary organs affected. Metastatic disease was reported in more than 100 cases in the literature.

KPC1-mediated ubiquitination and proteasomal processing of NF-κB1 p105 to p50 restricts tumor growth.

NF-κB is a key transcriptional regulator involved in inflammation and cell proliferation, survival, and transformation. Several key steps in its activation are mediated by the ubiquitin (Ub) system. One uncharacterized step is limited proteasomal processing of the NF-κB1 precursor p105 to the p50 active subunit.

Heparanase cooperates with Ras to drive breast and skin tumorigenesis.

Heparanase has been implicated in cancer but its contribution to the early stages of cancer development is uncertain. In this study, we utilized nontransformed human MCF10A mammary epithelial cells and two genetic mouse models [Hpa-transgenic (Hpa-Tg) and knockout mice] to explore heparanase function at early stages of tumor development. Heparanase overexpression resulted in significantly enlarged asymmetrical acinar structures, indicating increased cell proliferation and decreased organization.

Collision tumor of the mediastinum: a rare entity.

A collision tumor is a rare entity consisting of 2 different tumors that, because of proximity, merge together. The diagnosis of a collision tumor requires that the 2 tumors be histologically distinct. This phenomenon has been described mostly at the esophagogastric junction, where a squamous cell carcinoma of esophageal origin collides with a gastric adenocarcinoma.

Clinical significance of heparanase splice variant (t5) in renal cell carcinoma: evaluation by a novel t5-specific monoclonal antibody.

T5 is a novel splice variant of heparanase, an endo-β-D-glucuronidase capable of cleaving heparan sulfate side chains at a limited number of sites. T5 splice variant is endowed with pro-tumorigenic properties, enhancing cell proliferation, anchorage independent growth and tumor xenograft development despite lack of heparan sulfate-degrading activity typical of heparanase. T5 is over expressed in the majority of human renal cell carcinoma biopsies examined, suggesting that this splice variant is clinically relevant.