Anti-CD73 antibody therapy inhibits breast tumor growth and metastasis

Stagg, John; Divisekera, Upulie; McLaughlin, Nicole M.; Sharkey, Janelle; Pommey, Sandra; Denoyer, Delphine; Dwyer, Karen M.; Smyth, Mark J.

doi:10.1073/pnas.0908801107

Cited by 507 publications

(569 citation statements)

References 48 publications

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“…This result is in agreement with the literature that shows the increase of ecto-5′-NT/CD73 expression in many other cancers such as breast cancer, glioma, and melanoma [19,23,56]. Furthermore, ecto-5′-NT/CD73 overexpression promotes invasion, migration, adhesion, and metastasis of human breast cancer cells [20,57], indicating higher invasiveness and metastatic capability to melanomas [56,58] and poor prognosis in human colorectal cancer [22]. Ecto-5′-NT/CD73 expression in cancer cells has been also linked with drug resistance [26,59] and immune escape [44,60].…”

Section: Discussionsupporting

confidence: 93%

“…The final dephosphorylation of nucleotides, conversion of nucleoside monophosphates (e.g., AMP) to their respective nucleosides (e.g., adenosine), is catalyzed by ecto-5′-nucleotidase/CD73 (ecto-5′-NT/CD73). This enzyme is highly expressed in a variety of solid tumors [19][20][21][22] and has both its enzymatic activity and its adhesion protein function associated with cancer progression [23,24]. Besides, ecto-5′-NT/CD73 was found to be involved in cancer cell growth, maturation, differentiation, adhesion, migration, invasiveness, metastasis, immune escape, and drug resistance [19,[21][22][23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

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NTPDase3 and ecto-5′-nucleotidase/CD73 are differentially expressed during mouse bladder cancer progression

Rockenbach

Braganhol

Dietrich

et al. 2014

Purinergic Signalling

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According to the World Health Organization, bladder cancer is the seventh most common cancer among men in the world. The current treatments for this malignancy are not efficient to prevent the recurrence and progression of tumors. Then, researches continue looking for better therapeutic targets which can end up in new and more efficient treatments. One of the recent findings was the identification that the purinergic system was involved in bladder tumorigenesis. The ectonucleotidases, mainly ecto-5′-nucleotidase/CD73 have been revealed as new players in cancer progression and malignity. In this work, we investigated the NTPDase3 and ecto-5′-nucleotidase/CD73 expression in cancer progression in vivo. Bladder tumor was induced in mice by the addition of 0.05 % of N-butyl-N-(hydroxybutyl)-nitrosamine (BBN) in the drinking water for 4, 8, 12, 18, and 24 weeks. After this period, mice bladders were removed for histopathology analysis and immunofluorescence assays. The bladder of animals which has received BBN had alterations, mainly inflammation, in initial times of tumor induction. After 18 weeks, mice's bladder has developed histological alterations similar to human transitional cell carcinoma. The cancerous urothelium, from mice that received BBN for 18 and 24 weeks, presented a weak immunostaining to NTPDase3, in contrast to an increased expression of ecto-5′-nucleotidase/CD73. The altered expression of NTPDase3 and ecto-5′-nucleotidase/ CD73 presented herein adds further evidence to support the idea that alterations in ectonucleotidases are involved in bladder tumorigenesis and reinforce the ecto-5′-nucleotidase/ CD73 as a future biomarker and/or a target for pharmacological therapy of bladder cancer.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

NTPDase3 and ecto-5′-nucleotidase/CD73 are differentially expressed during mouse bladder cancer progression

Rockenbach

Braganhol

Dietrich

et al. 2014

Purinergic Signalling

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show abstract

“…Stagg et al and Zhou et al found that CD73, the ectoenzyme responsible for endogenous adenosine formation, contributes to breast cancer metastasis [15][16][17]. In agreement with these reports, we found that MDA-MB-231 cells overexpress CD73 and differ from HMEC in that they possess more efficient means than HMEC to hydrolyze extracellular ATP to adenosine (Fig.…”

Section: Discussionsupporting

confidence: 92%

“…Similarly, the ATP breakdown product adenosine can activate calcium signaling in MDA-MB-231 breast cancer cells, and the ectonucleotidase C D 7 3 , w h i c h c o n v e r t s e x t r a c e l l u l a r a d e n o s i n e monophosphate (AMP) to adenosine, was shown to promote breast cancer growth and metastasis [15][16][17]. In light of our previous work, these reports support the concept that purinergic signaling can indeed contribute to the motility and metastasis of breast cancer cells.…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

Adenosine arrests breast cancer cell motility by A3 receptor stimulation

Ledderose

Hefti

Chen

et al. 2016

Purinergic Signalling

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In neutrophils, adenosine triphosphate (ATP) release and autocrine purinergic signaling regulate coordinated cell motility during chemotaxis. Here, we studied whether similar mechanisms regulate the motility of breast cancer cells. While neutrophils and benign human mammary epithelial cells (HMEC) form a single leading edge, MDA-MB-231 breast cancer cells possess multiple leading edges enriched with A3 adenosine receptors. Compared to HMEC, MDA-MB-231 cells overexpress the ectonucleotidases ENPP1 and CD73, which convert extracellular ATP released by the cells to adenosine that stimulates A3 receptors and promotes cell migration with frequent directional changes. However, exogenous adenosine added to breast cancer cells or the A3 receptor agonist IB-MECA dose-dependently arrested cell motility by simultaneous stimulation of multiple leading edges, doubling cell surface areas and significantly reducing migration velocity by up to 75 %. We conclude that MDA-MB-231 cells, HMEC, and neutrophils differ in the purinergic signaling mechanisms that regulate their motility patterns and that the subcellular distribution of A3 adenosine receptors in MDA-MB-231 breast cancer cells contributes to dysfunctional cell motility. These findings imply that purinergic signaling mechanisms may be potential therapeutic targets to interfere with the motility of breast cancer cells in order to reduce the spread of cancer cells and the risk of metastasis.

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“…promoting functions in breast cancer (16). In breast-cancer cells, CD73 expression has been shown to be regulated by estrogen receptors (ER), whereby loss of ER significantly enhances CD73 expression (17).…”

Section: Discussionmentioning

confidence: 99%

Potential prognostic biomarker CD73 regulates epidermal growth factor receptor expression in human breast cancer

Zhi

Wang

et al. 2012

IUBMB Life

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SummaryCD73, an ecto-enzyme overexpressed in breast-cancer cells, catalyzes the dephosphorylation of adenosine monophosphates into adenosine. Anti-CD73 slows breast cancer growth and its spread both in vivo and in vitro. In this study, we investigated the relation of CD73 to epidermal growth factor receptor (EGFR) expression using tissue array and breast cancer cell lines. We found that CD73 expression correlated positively to EGFR expression in vivo (n 5 80, r 5 0.425, P \ 0.01) and in vitro. EGFR expression can be decreased by suppressing CD73 with an inhibitor or small shRNA, and this effect was reversed by adenosine and NECA (adenosine A2 receptor agonist), which suggested that adenosine is involved in EGFR expression regulated by CD73 (P \ 0.01). We also showed that CD73 regulates EGFR phosphorylation by Src (P \ 0.01). By transcription factor (TF) assay, CD73 was found to regulate some associated TFs activity such as PPARc, which mediates EGFR expression, although whether PPARc mediates the effect of CD73 on EGFR expression needs further study. The KaplanMeier recurrence-free survival curves for CD73 were also plotted in www.kmplot.com. The curves show that CD73 expression separates the cases into significantly different prognostic groups among the estrogen receptor-negative cancers (P \ 0.01). Our results suggest that CD73 may be a potential prognostic biomarker associated with coexpression of EGFR in human breast cancer.2012 IUBMB IUBMB Life, 64(11): 911-920, 2012

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Anti-CD73 antibody therapy inhibits breast tumor growth and metastasis

Cited by 507 publications

References 48 publications

NTPDase3 and ecto-5′-nucleotidase/CD73 are differentially expressed during mouse bladder cancer progression

NTPDase3 and ecto-5′-nucleotidase/CD73 are differentially expressed during mouse bladder cancer progression

Adenosine arrests breast cancer cell motility by A3 receptor stimulation

Potential prognostic biomarker CD73 regulates epidermal growth factor receptor expression in human breast cancer

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