Fibronectin expression in carcinoma cells correlates with tumor aggressiveness and poor clinical outcome in patients with invasive breast cancer

Bae, Young Kyung; Kim, Aeri; Kim, Min Kyoung; Choi, Jung Eun; Kang, Su Hwan; Lee, Soo Jung

doi:10.1016/j.humpath.2013.03.006

Cited by 141 publications

(136 citation statements)

References 24 publications

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“…Altered expression profiles of fibronectin, S100A4, HRAS and MMP9 in primary breast tissue have previously been shown to be associated with poor clinical outcome: high fibronectin expression has been linked with increased tumour aggressiveness and significantly reduced life expectancy (Bae et al 2013). Tissue array analysis of samples taken from 110 breast cancer patients has shown strong correlation between high fibronectin expression and higher probability of distant metastasis.…”

Section: Discussionmentioning

confidence: 99%

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Different molecular profiles are associated with breast cancer cell homing compared with colonisation of bone: evidence using a novel bone-seeking cell line

Nutter¹,

Holen²,

Brown³

et al. 2014

Endocrine-Related Cancer

106

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Advanced breast cancer is associated with the development of incurable bone metastasis. The two key processes involved, tumour cell homing to and subsequent colonisation of bone, remain to be clearly defined. Genetic studies have indicated that different genes facilitate homing and colonisation of secondary sites. To identify specific changes in gene and protein expression associated with bone-homing or colonisation, we have developed a novel bone-seeking clone of MDA-MB-231 breast cancer cells that exclusively forms tumours in long bones following i.v. injection in nude mice. Bone-homing cells were indistinguishable from parental cells in terms of growth rate in vitro and when grown subcutaneously in vivo. Only bone-homing ability differed between the lines; once established in bone, tumours from both lines displayed similar rates of progression and caused the same extent of lytic bone disease. By comparing the molecular profile of a panel of metastasis-associated genes, we have identified differential expression profiles associated with bone-homing or colonisation. Bone-homing cells had decreased expression of the cell adhesion molecule fibronectin and the migration and calcium signal binding protein S100A4, in addition to increased expression of interleukin 1B. Bone colonisation was associated with increased fibronectin and upregulation of molecules influencing signal transduction pathways and breakdown of extracellular matrix, including hRAS and matrix metalloproteinase 9. Our data support the hypothesis that during early stages of breast cancer bone metastasis, a specific set of genes are altered to facilitate bone-homing, and that disruption of these may be required for effective therapeutic targeting of this process.

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Section: Discussionmentioning

confidence: 99%

“…This work was funded by a University of Sheffield, UK, Research and Innovations grant awarded to Dr P D Ottewell (2010Ottewell ( -2012 and a Cancer Research UK Clinical Science Fellowship awarded to Dr J E Brown (2008-2013.…”

Section: Supplementary Datamentioning

confidence: 99%

Different molecular profiles are associated with breast cancer cell homing compared with colonisation of bone: evidence using a novel bone-seeking cell line

Nutter¹,

Holen²,

Brown³

et al. 2014

Endocrine-Related Cancer

106

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“…Over 60 integral membrane proteins contain an RGD sequence and could potentially bind streptavidin (12,15). Many of these proteins, such as integrins, VEGFA, angiopoietin, osteopontin, and fibronectin, have been shown to have a role in cancer development (16,17).…”

Section: Discussionmentioning

confidence: 99%

Streptavidin: A Novel Immunostimulant for the Selection and Delivery of Autologous and Syngeneic Tumor Vaccines

Weir

Hudson

Moon

et al. 2014

Cancer Immunology Research

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Induction of antitumor immunity using autologous tumor proteins is an attractive approach to cancer therapy. However, better methods and stimulants to present these autologous proteins back to the immune system are needed. Here, we identify streptavidin as a novel carrier protein and stimulant, and test the efficacy of both syngeneic (rat) and autologous vaccines (dogs) using streptavidin in combination with reduced soluble tumor proteins. Initial syngeneic vaccine studies in the 9L rat glioma model were used to optimize vaccine dose and selectivity. Cytokine and blood analysis was used to monitor the response. Rats receiving two vaccinations of syngeneic tumor vaccine demonstrated a statistically significant (P < 0.05) survival advantage compared with controls (adjuvant only). Notably, vaccination also led to remission rates of between 30% and 60% in the aggressive 9L glioma model. Antibodies to streptavidin were detected in the serum of vaccinated rats; however, antibody levels did not correlate with the response. The cytokine TNF-a was upregulated in vaccine-treated rats, whereas ICAM1 was downregulated. After engraftment, vaccinated rats maintained CD4þ T cells, and total lymphocyte levels closer to normal baseline than those in the controls. Twenty-five dogs treated with autologous vaccine preparations using streptavidin as a stimulant showed no adverse reactions, irrespective of additional chemotherapy and other medications. In this study, we developed a novel method for producing syngeneic and autologous vaccines using streptavidin selectivity and immunogenicity. These vaccines show efficacy in the 9L glioma rat model. Safety was also demonstrated in canine patients presenting with cancer treated with autologous vaccine.

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“…Similarly, some ECM signatures may only predict prognosis in certain subtypes: for example, SPARC mRNA level, though highest in luminal A tumors, predicts prognosis in basal and Her2 þ tumors, but not in luminal types [63], whereas fibronectin, highest in TNBC/basal or Her2þ tumors, has the highest prognostic value in hormone positive cancers [64]. Alternatively, in vitro work has suggested that ECM can alter expression subtype markers, further confounding the link to prognosis [65,66] As a result, studies with different clinical samples can show very different results, and caution is needed in interpreting findings.…”

Section: Breast Cancer Subtypesmentioning

confidence: 99%

The extracellular matrix in breast cancer predicts prognosis through composition, splicing, and crosslinking

Robertson

2016

Experimental Cell Research

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The extracellular matrix in breast cancer predicts prognosis through composition, splicing, and crosslinking a b s t r a c tThe extracellular matrix in the healthy breast has an important tumor suppressive role, whereas the abnormal ECM in tumors can promote aggressiveness, and has been linked to breast cancer relapse, survival and resistance to chemotherapy. This review article gives an overview of the elements of the ECM which have been linked to prognosis of breast cancers, including changes in ECM protein composition, splicing, and microstructure. Published by Elsevier Inc.

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Fibronectin expression in carcinoma cells correlates with tumor aggressiveness and poor clinical outcome in patients with invasive breast cancer

Cited by 141 publications

References 24 publications

Different molecular profiles are associated with breast cancer cell homing compared with colonisation of bone: evidence using a novel bone-seeking cell line

Different molecular profiles are associated with breast cancer cell homing compared with colonisation of bone: evidence using a novel bone-seeking cell line

Streptavidin: A Novel Immunostimulant for the Selection and Delivery of Autologous and Syngeneic Tumor Vaccines

The extracellular matrix in breast cancer predicts prognosis through composition, splicing, and crosslinking

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