Preferential up‐regulation of heparanase and cyclooxygenase‐2 in carcinogenesis of Barrett’s oesophagus and intestinal‐type gastric carcinoma

Sonoda, Ryotaro; Naomoto, Yoshio; Shirakawa, Yasuhiro; Fujiwara, Yasuhiro; Yamatsuji, Tomoki; Noma, Kazuhiro; Tanabe, Soichi; Takaoka, Munenori; Gündüz, Mehmet; Tsujigiwa, Hidetsugu; Nagatsuka, Hitoshi; Ohara, Nobuya; Yoshino, Tadashi; Takubo, Kaiyo; Tanaka, Noriaki

doi:10.1111/j.1365-2559.2010.03594.x

Cited by 18 publications

(15 citation statements)

References 46 publications

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“…Progression of Barrett’s esophagus to adenocarcinoma (Picardo et al, 2012); chronic gastritis to intestinal-type gastric carcinoma, chronic hepatitis C to hepatocellular carcinoma (Chiba et al, 2012); pancreatitis to pancreatic adenocarcinoma (Lowenfels et al, 1993) and colitis to colorectal cancer (Gupta et al, 2007) are well-known examples of inflammation-driven tumorigenesis. Remarkably, induction of heparanase prior to the appearance of malignancy was reported in essentially all of the above-mentioned inflammatory conditions, i.e., Barrett’s esophagus (Brun et al, 2009; Sonoda et al, 2010), hepatitis C infection (El-Assal et al, 2001), chronic pancreatitis (Koliopanos et al, 2001), Crohn disease and ulcerative colitis (Waterman et al, 2007 and Lerner et al, 2011). Given the causal role of heparanase in tumor progression in tissues in which cancer-related inflammation typically occurs [i.e., gastrointestinal tract, pancreas, liver (Brun et al, 2009; El-Assal et al, 2001; Hoffmann et al, 2008; Koliopanos et al, 2001; Naomoto et al, 2005; Nobuhisa et al, 2005; Sonoda et al, 2010; Xiong et al, 2012), it is conceivable that inflammation-induced heparanase may be involved in coupling inflammation and cancer.…”

Section: Heparanase In Acute and Chronic Inflammationmentioning

confidence: 99%

Heparanase: From basic research to therapeutic applications in cancer and inflammation

Vlodavsky¹,

Singh²,

Boyango³

et al. 2016

Drug Resistance Updates

192

229

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Heparanase, the sole heparan sulfate degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, angiogenesis and metastasis. Heparanase expression is enhanced in almost all cancers examined including various carcinomas, sarcomas and hematological malignancies. Numerous clinical association studies have consistently demonstrated that upregulation of heparanase expression correlates with increased tumor size, tumor angiogenesis, enhanced metastasis and poor prognosis. In contrast, knockdown of heparanase or treatments of tumor-bearing mice with heparanase-inhibiting compounds, markedly attenuate tumor progression further underscoring the potential of anti-heparanase therapy for multiple types of cancer. Heparanase neutralizing monoclonal antibodies block myeloma and lymphoma tumor growth and dissemination; this is attributable to a combined effect on the tumor cells and/or cells of the tumor microenvironment. In fact, much of the impact of heparanase on tumor progression is related to its function in mediating tumor-host crosstalk, priming the tumor microenvironment to better support tumor growth, metastasis and chemoresistance. The repertoire of the physiopathological activities of heparanase is expanding. Specifically, heparanase regulates gene expression, activates cells of the innate immune system, promotes the formation of exosomes and autophagosomes, and stimulates signal transduction pathways via enzymatic and non-enzymatic activities. These effects dynamically impact multiple regulatory pathways that together drive inflammatory responses, tumor survival, growth, dissemination and drug resistance; but in the same time, may fulfill some normal functions associated, for example, with vesicular traffic, lysosomal-based secretion, stress response, and heparan sulfate turnover. Heparanase is upregulated in response to chemotherapy in cancer patients and the surviving cells acquire chemoresistance, attributed, at least in part, to autophagy. Consequently, heparanase inhibitors used in tandem with chemotherapeutic drugs overcome initial chemoresistance, providing a strong rationale for applying anti-heparanase therapy in combination with conventional anti-cancer drugs. Heparin-like compounds that inhibit heparanase activity are being evaluated in clinical trials for various types of cancer. Heparanase neutralizing monoclonal antibodies are being evaluated in pre-clinical studies, and heparanase-inhibiting small molecules are being developed based on the recently resolved crystal structure of the heparanase protein. Collectively, the emerging premise is that heparanase expressed by tumor cells, innate immune cells, activated endothelial cells as well as other cells of the tumor microenvironment is a master regulator of the aggressive phenotype of cancer, an important contributor to the poor outcome of cancer patients and a prime target for therapy.

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Section: Heparanase In Acute and Chronic Inflammationmentioning

confidence: 99%

Heparanase: From basic research to therapeutic applications in cancer and inflammation

Vlodavsky¹,

Singh²,

Boyango³

et al. 2016

Drug Resistance Updates

192

229

View full text Add to dashboard Cite

show abstract

“…Progression of Barrett's oesophagus to adenocarcinoma (Picardo et al, 2012); chronic gastritis to intestinal-type gastric carcinoma, chronic hepatitis C to hepatocellular carcinoma (Chiba et al, 2012); pancreatitis to pancreatic adenocarcinoma (Lowenfels et al, 1993) and colitis to colorectal cancer (Gupta et al, 2007) are well-known examples of inflammation-driven tumorigenesis. Remarkably, induction of heparanase prior to the appearance of malignancy was reported in essentially all of the above-mentioned inflammatory conditions, i.e., Barrett's oesophagus (Brun et al, 2009; Sonoda et al, 2010), hepatitis C infection (El-Assal et al, 2001), chronic pancreatitis (Koliopanos et al, 2001), Crohn disease and ulcerative colitis (Lerner et al, 2011; Waterman et al, 2007). Given the causal role the enzyme plays in tumor progression in tissues in which cancer-related inflammation typically occurs [i.e., gastrointestinal tract, pancreas, liver (Brun et al, 2009; El-Assal et al, 2001; Hoffmann et al, 2008; Koliopanos et al, 2001; Naomoto et al, 2005; Nobuhisa et al, 2005; Sonoda et al, 2010; Xiong et al, 2012; Zhang et al, 2007)], it is conceivable that inflammation-induced heparanase may be involved in coupling inflammation and cancer.…”

Section: Heparanase In Inflammationmentioning

confidence: 99%

“…Remarkably, induction of heparanase prior to the appearance of malignancy was reported in essentially all of the above-mentioned inflammatory conditions, i.e., Barrett's oesophagus (Brun et al, 2009; Sonoda et al, 2010), hepatitis C infection (El-Assal et al, 2001), chronic pancreatitis (Koliopanos et al, 2001), Crohn disease and ulcerative colitis (Lerner et al, 2011; Waterman et al, 2007). Given the causal role the enzyme plays in tumor progression in tissues in which cancer-related inflammation typically occurs [i.e., gastrointestinal tract, pancreas, liver (Brun et al, 2009; El-Assal et al, 2001; Hoffmann et al, 2008; Koliopanos et al, 2001; Naomoto et al, 2005; Nobuhisa et al, 2005; Sonoda et al, 2010; Xiong et al, 2012; Zhang et al, 2007)], it is conceivable that inflammation-induced heparanase may be involved in coupling inflammation and cancer. The findings obtained in a study utilizing mouse model of colitis-associated colon carcinoma support this notion (Lerner et al, 2011).…”

Section: Heparanase In Inflammationmentioning

confidence: 99%

Versatile role of heparanase in inflammation

et al. 2013

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Heparanase is the only known mammalian endoglycosidase capable of degrading heparan sulfate glycosaminoglycan, both in extracellular space and within the cells. It is tightly implicated in cancer progression and over the past few decades significant progress has been made in elucidating the multiple functions of heparanase in malignant tumor development, neovascularization and aggressive behavior. Notably, current data show that in addition to its well characterized role in cancer, heparanase activity may represent an important determinant in the pathogenesis of several inflammatory disorders, such as inflammatory lung injury, rheumatoid arthritis and chronic colitis. Nevertheless, the precise mode of heparanase action in inflammatory reactions remains largely unclear and recent observations suggest that heparanase can either facilitate or limit inflammatory responses, when tissue/cell -specific contextual cues may dictate an outcome of heparanase action in inflammation. In this review the involvement of heparanase in modulation of inflammatory reactions is discussed through a few illustrative examples, including neuroinflammation, sepsis-associated lung injury and inflammatory bowel disease. We also discuss possible action of the enzyme in coupling inflammation and tumorigenesis in the setting of inflammation-triggered cancer.

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“…COX-2 expression is more prominent in intestinaltype gastric cancer when compared to the diffuse type (21,22). Ma et al (23) reported that COX-2 expression is essential for the survival and proliferation of gastric cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Assessment of COX-2 expression presence and severity by immunohistochemical method in patients with chronic active gastritis and intestinal metaplasia

Erkan

Gönül²,

Kandılcı³

et al. 2012

Turk J Gastroenterol

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Preferential up‐regulation of heparanase and cyclooxygenase‐2 in carcinogenesis of Barrett’s oesophagus and intestinal‐type gastric carcinoma

Abstract: HPSE and COX-2 are preferentially up-regulated in Barrett's oesophagus and intestinal-type GC. These molecules may play an important role during the development of inflammation-related adenocarcinoma of the upper gastrointestinal tract.

Cited by 18 publications

References 46 publications

Heparanase: From basic research to therapeutic applications in cancer and inflammation

Heparanase: From basic research to therapeutic applications in cancer and inflammation

Versatile role of heparanase in inflammation

Assessment of COX-2 expression presence and severity by immunohistochemical method in patients with chronic active gastritis and intestinal metaplasia

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