Tamoxifen decreases extracellular TGF-β1 secreted from breast cancer cells — A post-translational regulation involving matrix metalloproteinase activity

Nilsson, Ulrika Wilhelmina; Jönsson, Jill; Dabrosin, Charlotta

doi:10.1016/j.yexcr.2008.10.015

Cited by 25 publications

(20 citation statements)

References 34 publications

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“…Many cell types, including immune cells, produce TGFb1, which is secreted in a latent form bound to various proteins (45). Events in the microenvironment, such as protease activities, release active TGFb1 into the extracellular fluid where it becomes available for cell-cell interactions (19). A correlation between TGFb1 and increased metastasis has previously been shown only by immunostaining human breast cancers.…”

Section: Discussionmentioning

confidence: 99%

“…Cross-talk between TGFb1 and estradiol (E 2 ) in breast cancer has been reported; for instance, TGFb1 and E 2 together enrich cancer stem cell populations in breast tumors, leading to increased migration and drug and radiation resistance (18). Estradiol also increases TGFb1 secretion in experimental breast cancers both in vitro and in vivo (19). Cellcell interactions in tumor microenvironments can be enhanced by integrins, which play a major role in cancer cell proliferation and metastasis (20,21).…”

Section: Introductionmentioning

confidence: 99%

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Estradiol Promotes Breast Cancer Cell Migration via Recruitment and Activation of Neutrophils

Rodriguez

Abrahamsson

Jensen

et al. 2017

Cancer Immunology Research

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Estradiol (E 2 ) plays a key role in breast cancer progression. Most breast cancer recurrences express the estrogen receptor (ER), but nearly 50% of patients are resistant to antiestrogen therapy. Novel therapeutic targets of ER-positive breast cancers are needed. Protumoral neutrophils expressing the lymphocyte functionassociated antigen 1 (LFA-1) integrin may mediate cancer metastasis, and TGFb1 is the major chemoattractant for neutrophils. The role of E 2 in neutrophil-ER þ breast cancer cell interactions is unknown. We studied this in vivo using murine breast cancers in immunocompetent mice and human breast cancers in nude mice. Cell dissemination was evaluated in a zebrafish model, and microdialysis of breast cancer patients was performed. In vitro studies were done with mammosphere cultures of breast cancer cells and human neutrophils. We found that E 2 increased the number of LFA-1 þ neutrophils recruited to the invasive edge of mouse tumors, increased TGFb1 secretion and promoted neutrophil infiltration in mammospheres, and induced overexpression of LFA-1 in neutrophils. In zebrafish, in the presence of E 2 , neutrophils increased dissemination of ER þ breast cancer cells via LFA-1 and TGFb1, thus causing noninvasive cancer cells to be highly metastatic. Time-lapse imaging in zebrafish revealed close interactions of neutrophils with cancer cells, which drove breast cancer metastasis. We also found that extracellular TGFb1 was overproduced in human breast cancer tissue compared with adjacent normal breast tissue. Thus, E 2 can regulate immune/cancer cell interactions in tumor microenvironments. Our results indicate that extracellular TGFb1 is a relevant target in human breast cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Estradiol Promotes Breast Cancer Cell Migration via Recruitment and Activation of Neutrophils

Rodriguez

Abrahamsson

Jensen

et al. 2017

Cancer Immunology Research

Self Cite

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“…Although the mechanisms of the estrogen receptor-independent effects of TAM remain a subject of debate (9), it is clear from a large body of literature that TAM has a wide range of effects on mammalian cell physiology, including antioxidant activity (47,48), antiangiogenesis properties (43), the stimulation of transforming growth factor beta secretion (28), the induction of intracellular calcium release (14), the alteration of cellular membrane properties (47), and the induction of apoptosis (2). Consistent with this plethora of cellular effects, TAM has been shown to target a number of proteins in mammalian cells, including calmodulin, protein kinase C, phospholipase C, phosphoinositide kinase, P-glycoprotein, and swell-induced chloride channels (9).…”

mentioning

confidence: 99%

Antifungal Activity of Tamoxifen: In Vitro and In Vivo Activities and Mechanistic Characterization

Dolan

Montgomery²,

Buchheit³

et al. 2009

Antimicrob Agents Chemother

106

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Tamoxifen (TAM), an estrogen receptor antagonist used primarily to treat breast cancer, has well-recognized antifungal properties, but the activity of TAM has not been fully characterized using standardized (i.e., CLSI) in vitro susceptibility testing, nor has it been demonstrated in an in vivo model of fungal infection. In addition, its mechanism of action remains to be clearly defined at the molecular level. Here, we report that TAM displays in vitro activity (MIC, 8 to 64 g/ml) against pathogenic yeasts (Candida albicans, other Candida spp., and Cryptococcus neoformans). In vivo, 200 mg/kg of body weight per day TAM reduced kidney fungal burden (؊1.5 log 10 CFU per g tissue; P ‫؍‬ 0.008) in a murine model of disseminated candidiasis. TAM is a known inhibitor of mammalian calmodulin, and TAM-treated yeast show phenotypes consistent with decreased calmodulin function, including lysis, decreased new bud formation, disrupted actin polarization, and decreased germ tube formation. The overexpression of calmodulin suppresses TAM toxicity, hypofunctional calmodulin mutants are hypersensitive to TAM, and TAM interferes with the interaction between Myo2p and calmodulin, suggesting that TAM targets calmodulin as part of its mechanism of action. Taken together, these experiments indicate that the further study of compounds related to TAM as antifungal agents is warranted.

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“…All these potential regulatory mechanisms together or alone may lead to an impaired PMN influx to the sites of inflammation in MMP-8 deficient mice and alter disease expression. Similarly, MMP-9 activity was shown to down regulate TGF-1 protein levels in breast cancer cells exposed to tamoxifen (Nilsson, Jonsson, and Dabrosin 2009;Balbin et al 2003). In addition, recent evidence supports that MMP-13 might also influence soluble protein levels from RANKL/OPG axis (Nannuru et al 2010).…”

Section: Matrix Metalloproteinases (Mmps): Destructive Versus Regulatmentioning

confidence: 91%

“…Accordingly, several studies support a role for MMP-8 in PMN trafficking in different inflammation models. LIX/CXCL5 levels have also shown to diminish in other MMP-8 knock-out mouse models (Gutierrez-Fernandez et al 2007;Nilsson, Jonsson, and Dabrosin 2009), such as TNF-induced lethal hepatitis model (Van Lint et al 2005), and reduced levels of transforming growth factor (TGF)-1 in MMP-8 -/-mice have been associated with PMN impaired infiltration and wound healing (GutierrezFernandez et al 2007). All these potential regulatory mechanisms together or alone may lead to an impaired PMN influx to the sites of inflammation in MMP-8 deficient mice and alter disease expression.…”

Section: Matrix Metalloproteinases (Mmps): Destructive Versus Regulatmentioning

confidence: 99%

The Role of Immuno-Inflammatory Response in the Pathogenesis of Chronic Periodontitis and Development of Chair-Side Point of Care Diagnostics

Hernández

Vernal²,

Sorsa³

et al. 2012

Pathogenesis and Treatment of Periodontitis

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Tamoxifen decreases extracellular TGF-β1 secreted from breast cancer cells — A post-translational regulation involving matrix metalloproteinase activity

Cited by 25 publications

References 34 publications

Estradiol Promotes Breast Cancer Cell Migration via Recruitment and Activation of Neutrophils

Estradiol Promotes Breast Cancer Cell Migration via Recruitment and Activation of Neutrophils

Antifungal Activity of Tamoxifen: In Vitro and In Vivo Activities and Mechanistic Characterization

The Role of Immuno-Inflammatory Response in the Pathogenesis of Chronic Periodontitis and Development of Chair-Side Point of Care Diagnostics

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