Searchable abstracts of presentations at key conferences on calcified tissues
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43rd Annual European Calcified Tissue Society Congress

Rome, Italy
14 May 2016 - 17 May 2016

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ba0005cabs.oc1.1 | Oral Communications | ECTS2016

Secreted YB-1 (Y-box binding protein 1) as a biomarker of bone disease progression in patients with breast cancer and bone metastases

Bettencourt Maria , Ferreira Arlindo , Alho Irina , Lucia Costa Ana , Sousa Ana Rita , Mansinho Andre , Abreu Catarina , Pulido Catarina , Macedo Daniela , Vendrell Ines , Pacheco Teresa , Costa Luis , Casimiro Sandra

YB-1 (Y-box binding protein 1) is a multifunctional cold-shock protein that has been implicated in all hallmarks of cancer. Elevated YB-1 protein levels were correlated with poor prognosis in several types of cancers, including breast cancer (BC). In BC, high YB-1 expression is a marker of decreased overall survival (OS) and distant metastasis-free survival across all subtypes. YB-1 is also secreted by different cell types and may act as an extracellular mitogen. Therefore, ou...

ba0005cabs.oc1.2 | Oral Communications | ECTS2016

Bone and metabolic parameters are associated with overall survival in patients with bone metastases from adenocarcinoma lung cancer: the POUMOS study

Confavreux Cyrille B. , Chambard Lauriane , Ollier Edouard , Brevet Marie , Duboeuf Francois , Rousseau Jean-Charles , Pialat Jean-Baptiste , Wegrzyn Julien , Tescaru Agnes , Szulc Pawel , Carlier Marie-Christine , Girard Nicolas , Clezardin Philippe

Rational: Mortality due to non-small cell lung cancers is the first cause of cancer death in men around the world. Lung adenocarcinoma regularly induces bone metastases responsible for high morbidity and impaired life quality. Overall survival of these patients is poor. Thus we aimed to identify if some bone and metabolic parameters were associated with overall survival.Patients and Methods: POUMOS is a prospective cohort of patients suffering from adeno...

ba0005cabs.oc1.3 | Oral Communications | ECTS2016

Blocking IL-1R signalling inhibits breast cancer growth and bone metastases by altering the tumour microenvironment

Bradbury Steven , Rennicks Sarah , Evans Alyson , del Carmen Basitdas Mary , Holen Ingunn , Ottewell Penelope

Background: We have recently identified interleukin 1B (IL-1B) as a potential biomarker for predicting breast cancer patients at increased risk for developing bone metastasis. In mouse models, IL-1B and its receptor (IL-1R1) are upregulated in breast cancer cells that metastasise to bone compared with cells that do not. We have now investigated whether blocking IL-1R with the clinically licensed antagonist, anakinra, might be a potential treatment for breast cancer and bone me...

ba0005cabs.oc2.1 | Oral Communications | ECTS2016

Prostate cancer microRNAs in extracellular vesicles stimulate osteoclastogenesis

Bijnsdorp Irene , Mulder Jorn , Geldof Albert , Bakker Astrid , de Vries Teun , van Moorselaar Jeroen

Prostate cancer (PCa) is the most common cancer in males. When patients develop metastasis, no curative therapy is available. To find new therapeutic options, it is crucial to understand how PCa cells induce metastasis. Recently, it was shown that PCa cells secrete small extracellular vesicles (EVs) that can be found in the circulation and in bones. Uptake of EVs by other cells may change their behaviour. We previously identified three miRNAs that were uniquely upregulated in ...

ba0005cabs.oc2.2 | Oral Communications | ECTS2016

Integrin α5 is an independent prognosis factor and a potential therapeutic target for breast cancer bone metastasis

Pantano Francesco , Croset Martine , Driouch Keltouma , Bonnelye Edith , Bednarz-Knoll Natalia , Hong Saw-See , Iuliani Michele , Fioramonti Marco , Santini Daniele , Tonini Giuseppe , Pantel Klaus , Clezardin Philippe

Aims: Using an extensive bioinformatic approach we identified integrin α5 subunit as a novel potential target to treat bone dissemination from breast cancer. Aim of this study is to confirm the value of this target.Methods: Integrin α5 mRNA expression levels were quantified by qRT-PCR, using radically resected primary tumors of 427 breast cancer patients. α5 expression at protein level by IHC on primary tumor was correlated, in an addition...

ba0005cabs.oc2.3 | Oral Communications | ECTS2016

Cancer cell homing to the bone marrow is modulated by the mesenchymal stromal cell

Rossnagl Stephanie , Nakchbandi Inaam

Several cell types form the hematopoietic stem cell niche. These niches sometimes become hijacked by cancer cells, which may later form metastatic lesions. Our aim was therefore to characterize the bone marrow microenvironment to affect cancer cell homing to bone marrow.Pharmacologic modification consisting of PTH to stimulate the osteoblasts and zoledronic acid to prevent the increase in osteoclasts through PTH resulted in increased homing of cancer cel...

ba0005cabs.oc2.4 | Oral Communications | ECTS2016

Peripheral tumour re-growth following combination therapy – role of the bone microenvironment

Haider Marie-Therese , Ottewell Penelope D. , Brown Nicola J. , Lefley Diane V. , Holen Ingunn

Background: Cancer patients often receive a combination of drugs that target both the microenvironment and the tumour cells. However, the role of the bone microenvironment (BME) in mediating peripheral breast cancer growth remains poorly understood. This is the first study to determine whether reduced subcutaneous tumour growth following combination therapy is due to direct interactions between the drugs and tumour cells or through zoledronic acid induced alterations to the BM...

ba0005cabs.oc2.5 | Oral Communications | ECTS2016

Inhibition of BMP signalling reduces bone destruction and impacts niche maintenance in a mouse model of multiple myeloma

Gooding Sarah , Webb Siobhan , Olechnowicz Sam , Lwin Seint , Armitage Andrew , Ramasamy Karthik , Drakesmith Hal , Edwards Claire

Multiple myeloma is usually incurable, the bone marrow niche providing a protective microenvironment for quiescent tumour cells. We hypothesised that manipulation of BMP activity, a regulator of cell differentiation in the bone marrow, might affect control of tumour growth by its niche and in addition alter the lytic bone disease of myeloma. Moreover BMP signalling contributes to the hepcidin upregulation and resultant inflammatory anaemia that is characteristic of myeloma. Re...

ba0005cabs.oc3.1 | Oral Communications | ECTS2016

Blockade of C5aR impairs tumor-induced osteoclastogenesis preventing bone metastasis colonization in lung cancer

Ajona Daniel , Zandueta Carolina , Corrales Leticia , Pajares Maria J. , Martinez-Terroba Elena , Perurena Naiara , Montuenga Luis M. , Pio Ruben , Lecanda Fernando

C5aR is a membrane-associated receptor for C5a, a potent immune mediator generated after complement activation. C5aR expressed in tumor infiltrating immune cells creates a favorable microenvironment for tumor progression. However, the expression of C5aR by cancer cells and its contribution to their malignant phenotype is poorly understood. Immunohistochemical analysis revealed that high levels of C5aR in human lung tumors were associated with poor survival (P=0.005) a...

ba0005cabs.oc3.2 | Oral Communications | ECTS2016

Osteoblasts inhibit the immune response against cancer

Rossnagl Stephanie , Kraft Sabrina , Sens Carla , Nakchbandi Inaam

Osteoblasts line the inner surface of the bone and are located in close proximity to the bone marrow, where hematopoiesis takes place. Osteoblasts produce several cytokines that affect various steps of hematopoiesis, and produce fibronectin isoforms that affect cell differentiation. Little is known however on whether osteoblasts modulate the immune response. Our aim was to evaluate the role of fibronectin originating from the osteoblasts on hematopoiesis and the immune respons...

ba0005cabs.oc3.3 | Oral Communications | ECTS2016

Visualizing the tumor immunity in living bone marrow by intravital 2-photon imaging

Yamashita Erika , Mizuno Hiroki , Ishii Masaru

Within a living organism, the adaptive immune system, e.g. cytotoxic T lymphocytes (CTLs), induce apoptosis in tumor cells, and therefore limit tumor development. Bone marrow is a mysterious hidden place for different tumor cells and the anti-tumor immunity in the bone marrow is important because the specific microenvironment had been considered to contribute to escape of tumor cells from immune attack. However, the practical mechanism of anti-tumor immune elimination by CTLs ...

ba0005cabs.oc3.4 | Oral Communications | ECTS2016

Anti-sclerostin treatment prevents multiple myeloma bone disease and reduces tumour burden

McDonald Michelle , Reagan Michaela , Terry Rachael , Pettitt Jessica , Le Lawrence , Mohanty Sindhu , Kramer Ina , Kneissel Michaela , Brooks Daniel , Cheng Tegan , Little David , Bouxsein Mary , Rosen Cliff , Ghobrial Irene , Croucher Peter

Multiple myeloma is characterized by extensive bone marrow tumour and destructive osteolytic lesions. Both increased bone resorption and suppressed bone formation result in lesions and pathological fractures. Anti-resorptive therapies prevent further bone loss but patients continue to fracture, arguing for new therapies which increase bone strength. Anti-Sclerostin (Anti-Scl) is a potent stimulator of bone formation, is currently in clinical trials for osteoporosis, however it...

ba0005cabs.oc3.5 | Oral Communications | ECTS2016

Targeting skeletal metastatic breast cancer with bisphosphonic matrix metalloproteinase-2 inhibitors

Tauro Marilena , Laghezza Antonio , Paolo Tortorella , Lynch Conor

Breast to bone metastasis is a common incurable event during breast cancer progression. Identifying the molecular mechanisms at play is vital for the development of new therapies. Matrix metalloproteinases, such as MMP-2, are overexpressed in the bone metastatic microenvironment. Genetic ablation of MMP-2 demonstrated its importance of in driving osteolytic bone metastatic breast cancer and support the rationale for the development of a highly specific MMP-2 inhibitor for the ...

ba0005cabs.oc4.1 | Oral Communications | ECTS2016

Muscle dysfunction in immune competent mice with osteolytic breast cancer in bone is associated with skeletal muscle oxidation of RyR1

Regan Jenna , Waning David , Mohammad Khalid , Mikesell Carter , Reiken Steven , Marks Andrew , Guise Theresa

Cancer-associated muscle weakness is an important paraneoplastic syndrome for which there is currently no treatment. Human breast cancer bone metastases (MDA-MB-231 cells in immune deficient mice) induce extensive bone destruction, leading to the release of TGF-β from the bone matrix. We have previously shown that bone-derived TGF-β is responsible for muscle weakness in this model. Mechanistically, TGF-β signaling increases the expression of NADPH oxidase 4 (Nox...

ba0005cabs.oc4.2 | Oral Communications | ECTS2016

Bisphosphonates prevent osteolysis and muscle weakness in aromatase inhibitor-treated mice with breast cancer bone metastases

Wright Laura , Harhash Ahmed , Waning David , Mohammad Khalid , Marks Andrew , Guise Theresa

Up to half of women treated with an aromatase inhibitor (AI) for breast cancer develop muscle weakness, bone loss, and joint pain. Moreover, an elevated state of osteoclastic bone resorption has been shown to prime the bone microenvironment in ways that accelerate metastatic growth. We hypothesized that AI-induced bone loss could increase breast cancer progression in bone and exacerbate muscle weakness associated with bone metastases. Four-week female athymic nude mice underwe...

ba0005cabs.oc4.3 | Oral Communications | ECTS2016

In vitro mechanotransduction of osteosarcoma cells

Coughlin Thomas R. , Gadi Abhilash , Mansukhani Alka , Kennedy Oran D.

Osteosarcoma is a heterogeneous tumor from the mesenchymal lineage, and is the most common form of primary bone cancer. Normally, lesions contain undifferentiated cancer stem cells (CSCs) that support uncontrolled growth/proliferation, and pre-osteoblasts that form excessive amounts of immature bone. CSCs are characterized by high expression of the transcriptional regulators Sox2 and yes-associated protein (YAP) that are essential for tumorigenicity. YAP is restrained by the H...

ba0005cabs.oc4.4 | Oral Communications | ECTS2016

3D tissue engineered constructs for modeling tumor-induced bone disease

Dadwal Ushashi , Guo Ruijing , Lu Sichang , Vanderburgh Joseph , Merkel Alyssa , Kwakwa Kristin , Guelcher Scott , Sterling Julie

While the importance of interactions between bone and tumors is well-established, the mechanism by which the physical bone microenvironment regulates disease progression is limited by the lack of suitable in vitro models. We have designed 3D Tissue Engineered Constructs (TECs) using microCT imaging in tandem with inkjet 3D printing technology that recapitulate the mechanical and morphometric properties of trabecular bone. 3D-printed TECs exhibited no significant diffe...

ba0005cabs.oc4.5 | Oral Communications | ECTS2016

New models of breast and lung cancer bone metastases for preclinical efficacy testing

Suominen Mari I. , Hagemann Urs B. , Konkol Yvonne , Bernoulli Jenni , Fagerlund Katja M. , Bjerke Roger M. , Karlsson Jenny , Halleen Jussi M. , Cuthbertson Alan

In advanced ER+ve breast cancer, the propensity of bone involvement is 85%. Similarly in advanced lung cancer, 30–40% of patients develop bone metastases, and as recent advances in lung cancer therapies improve survival, the number of patients living with bone metastases is expected to increase. At the same time there is a paucity of especially ER+ and osteoblastic animal models available. We present herein the development of four mouse models of breast and lung cancer su...