Expression of matrix macromolecules and functional properties of breast cancer cells are modulated by the bisphosphonate zoledronic acid

Dedes, Petros G.; Gialeli, Ch.; Tsonis, Anastasios; Kanakis, Ioannis; Theocharis, Achilleas D.; Kletsas, Dimitris; Tzanakakis, George N.; Karamanos, Nikos K.

doi:10.1016/j.bbagen.2012.07.013

Cited by 76 publications

(54 citation statements)

References 74 publications

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“…ZOL is shown to inhibit migration and invasion of ER-ve breast cancer cells but has comparatively modest inhibitory effects on ER?ve cells in vitro [36][37][38]. In agreement with this, we found no effects of ZOL on migration or invasion of MCF7 or T47D cells in vitro (data not shown).…”

Section: Discussionsupporting

confidence: 80%

Oestrogen receptor positive breast cancer metastasis to bone: inhibition by targeting the bone microenvironment in vivo

Holen

Walker

Nutter

et al. 2015

Clin Exp Metastasis

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Clinical trials have shown that adjuvant Zoledronic acid (ZOL) reduces the development of bone metastases irrespective of ER status. However, postmenopausal patients show anti-tumour benefit with ZOL whereas pre-menopausal patients do not. Here we have developed in vivo models of spontaneous ER?ve breast cancer metastasis to bone and investigated the effects of ZOL and oestrogen on tumour cell dissemination and growth. ER?ve (MCF7, T47D) or ER-ve (MDA-MB-231) cells were administered by inter-mammary or inter-cardiac injection into female nude mice ± estradiol. Mice were administered saline or 100 lg/kg ZOL weekly. Tumour growth, dissemination of tumour cells in blood, bone and bone turnover were monitored by luciferase imaging, histology, flow cytometry, two-photon microscopy, micro-CT and TRAP/P1NP ELISA. Estradiol induced metastasis of ER?ve cells to bone in 80-100 % of animals whereas bone metastases from ER-ve cells were unaffected. Administration of ZOL had no effect on tumour growth in the fat pad but significantly inhibited dissemination of ER?ve tumour cells to bone and frequency of bone metastasis. Estradiol and ZOL increased bone volume via different mechanisms: Estradiol increased activity of bone forming osteoblasts whereas administration of ZOL to estradiol supplemented mice decreased osteoclast activity and returned osteoblast activity to levels comparable to that of saline treated mice. ER-ve cells require increased osteoclast activity to grow in bone whereas ER?ve cells do not. Zol does not affect ER?ve tumour growth in soft tissue, however, inhibition of bone turnover by ZOL reduced dissemination and growth of ER?ve breast cancer cells in bone.

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Section: Discussionsupporting

confidence: 80%

Oestrogen receptor positive breast cancer metastasis to bone: inhibition by targeting the bone microenvironment in vivo

Holen

Walker

Nutter

et al. 2015

Clin Exp Metastasis

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“…Thus, they should be considered as possible anti-cancer agents. This reasoning is supported by the ability of these compounds to suppress proliferation of cancer cells of prostate, [119] breast, [120,121] melanoma, [122] ovarian [123] and colorectal cancers, [124] as well as glioblastoma [125] and multiple myelanoma [126]. Additionally these drugs have also been shown to kill cancers in humans independently on their action on bones.…”

Section: Anti-cancer Activitymentioning

confidence: 59%

Physiologic Activity of Bisphosphonates – Recent Advances

Chmielewska¹,

Kafarski

2016

PHARMSCI

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“…Recent studies also showed that doxycycline inhibited activity of gelatinases and diminished tumor growth, invasion and metastasis in osteosarcoma, and lung, ovarian, cervical and oral cancer cell lines [39][40][41][42]. Similarly, zoledronate, which is nitrogen-containing bisphosphonate, exerts antitumoral effects by suppressing MMP expression and/or activity in various cancers [43,44]. Recently, we have also reported that zoledronate downregulated MMP-2 and -9 expression and activities in PC3 prostate cancer cells [45].…”

Section: Discussionmentioning

confidence: 92%

Doxycycline down-regulates matrix metalloproteinase expression and inhibits NF-κB signaling in LPS-induced PC3 cells

Ogut

Reel

Korkmaz

et al. 2017

Folia Histochem Cytobiol.

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Introduction. Matrix metalloproteinase enzymes (MMPs) play important role in inflammation, malignant cell proliferation, invasion and angiogenesis by mediating extracellular matrix degradation. Doxycycline, a synthetic tetracycline, behaves as a MMP inhibitor at a subantimicrobial dose and inhibits tumor cell proliferation, invasion and angiogenesis. The aberrant activity of nuclear factor kappa B (NF-kB) causes activation of MMPs and thereby proliferation and invasion of cancer cells. The aim of this study was to investigate the effects of doxycycline on the expression of MMPs in lipopolysaccharide (LPS)-induced PC3 human prostate cancer cells and the possible role of NF-kB signaling. Material and methods. PC3 cells were incubated with LPS (0.5 µg/mL) for 24 h in the presence or absence of doxycycline (5 µg/mL). The effects of LPS and doxycycline on the expressions of MMP-2, MMP-8, MMP-9, MMP-10, NF-kB/p65, IkB-a, p-IkB-a, IKK-b were examined by Western blotting and immunohistochemistry in PC3 cells. Furthermore, relative proteinase activities of MMP-2 and MMP-9 were determined by gelatin zymography. Results. LPS increased expression and activity of MMP-9 and expression of MMP-8, MMP-10, NF-kB/p65, p-IkB-a, IKK-b and doxycycline down-regulated its effects with the exception of MMP-10 expression. The expression of MMP-2 and IkB-a was affected by neither LPS nor doxycycline. Conclusions. Our findings indicate that doxycycline inhibits the expression of various MMPs and NF-kB signaling may play a role in the regulation of MMPs expression in LPS-induced PC3 human prostate cancer cells.

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Expression of matrix macromolecules and functional properties of breast cancer cells are modulated by the bisphosphonate zoledronic acid

Cited by 76 publications

References 74 publications

Oestrogen receptor positive breast cancer metastasis to bone: inhibition by targeting the bone microenvironment in vivo

Oestrogen receptor positive breast cancer metastasis to bone: inhibition by targeting the bone microenvironment in vivo

Physiologic Activity of Bisphosphonates – Recent Advances

Doxycycline down-regulates matrix metalloproteinase expression and inhibits NF-κB signaling in LPS-induced PC3 cells

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