Relaxin Stimulates Bronchial Epithelial Cell PKA Activation, Migration, and Ciliary Beating<sup>1</sup>

Wyatt, Todd A.; Sisson, Joseph H.; Forgèt, Mary A.; Bennett, Robert G.; Hamel, Frederick G.; Spurzem, John R.

doi:10.1177/153537020222701114

Cited by 24 publications

(17 citation statements)

References 41 publications

(36 reference statements)

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“…Relaxin has previously been identified as a hormone promoting the motility of human and canine mammary carcinoma cell lines (human, MCF-7 and SK-BR3; canine, CF33.Mt) 15,32 as well as noncarcinogenic bronchial epithelial cells and inflammatory cells infiltrating wounds. 33, 34 Here we demonstrate that both recombinant RLN2 and secreted proRLN2 profoundly accelerated the cellular motility of two human thyroid carcinoma cell lines (FTC-133 and FTC-238) and the corresponding RLN2 transfectants in an autocrine/ paracrine LGR7-dependent manner. The ability to promote tumor cell motility appears to be characteristic for both relaxin members, relaxin and INSL3, because INSL3 can also act as a motility-enhancing factor on PC-3 human prostate carcinoma cells.…”

Section: Discussionmentioning

confidence: 97%

Relaxin Enhances the Oncogenic Potential of Human Thyroid Carcinoma Cells

Hombach‐Klonisch

Białek

Trojanowicz

et al. 2006

The American Journal of Pathology

102

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The role of members of the insulin-like superfamily in human thyroid carcinoma is primarily unknown. Here we demonstrate the presence of RLN2 relaxin and relaxin receptor LGR7 in human papillary, follicular, and undifferentiated anaplastic thyroid carcinoma suggesting a specific involvement of relaxin-LGR7 signaling in thyroid carcinoma. Stable transfectants of the LGR7-positive human follicular thyroid carcinoma cell lines FTC-133 and FTC-238 that secrete bioactive proRLN2 revealed this hormone to act as a multifunctional endocrine factor in thyroid carcinoma cells. Although RLN2 did not act as a mitogen, it acted as an autocrine/paracrine factor and significantly increased anchorage-independent growth and thyroid carcinoma cell motility and invasiveness through elastin matrices. In recent years, the multifunctional peptide hormone relaxin has been identified as an important endocrine player in the reproductive tract, cardiovascular/neural systems, and oncology.1,2 The thyroid was once considered to be a relaxin target tissue with relaxin reported to increase thyroid weight, radioactive iodine uptake, and protein-bound iodination in rats.3,4 Likely because of the crude relaxin preparations used at the time, these results could not be confirmed. 5 No further investigations were reported thereafter using highly purified relaxin preparations to validate a potential role of relaxin in thyroid tissues and thyroid cell lines. Some 40 years later, the discovery of the G-protein-coupled relaxin-like receptors LGR7 and LGR8 revealed the presence of transcripts for both LGR7 (relaxin receptor) and LGR8 (INSL3/relaxin receptor) in the thyroid gland. 6 -8 Relaxin and the relaxin-like INSL3 have been shown to activate cAMP-dependent signaling pathways by binding to either LGR7 or LGR8. 8 -12 We recently demonstrated the expression and regulation of INSL3 and LGR8 transcripts in human thyroid carcinoma cell lines, identifying hyper-and neoplastic human thyrocytes as a new source and target of the actions of INSL3 and a novel INSL3 splice variant. 8,13 Although still primarily undefined, relaxin appears to have oncogenic potential in various organs and tissues, including the human thyroid.14 -17 Relaxin affects proliferation and differentiation of MCF-7 human carcinoma cells in a concentration-dependent manner 18 and can modify the extracellular matrix by affecting the expresSupported by the Deutsche Forschungsgemeinschaft (grants KL1249/5-1

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Section: Discussionmentioning

confidence: 97%

Relaxin Enhances the Oncogenic Potential of Human Thyroid Carcinoma Cells

Hombach‐Klonisch

Białek

Trojanowicz

et al. 2006

The American Journal of Pathology

102

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“…Relaxin has been shown to inhibit the TGF-b-induced expression of both collagen and fibronectin in human lung fibroblasts, as well as inducing levels of MMP-1 [213]. The hormone also stimulated wound healing of bronchial epithelial cells in vitro [214] and, in a murine model, relaxin restored bleomycin-induced collagen accumulation back to normal levels [213].…”

Section: Contribution Of Tgf-b and Egf To Remodelling C Boxall Et Almentioning

confidence: 97%

The contribution of transforming growth factor- and epidermal growth factor signalling to airway remodelling in chronic asthma

Boxall

Holgate²,

Davies³

2006

European Respiratory Journal

225

187

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Asthma is increasing in prevalence in the developing world, affecting ,10% of the world's population. It is characterised by chronic lung inflammation and airway remodelling associated with wheezing, shortness of breath, acute bronchial hyperresponsiveness to a variety of innocuous stimuli and a more rapid decline in lung function over time.Airway remodelling, involving proliferation and differentiation of mesenchymal cells, particularly myofibroblasts and smooth muscle cells, is generally refractory to corticosteroids and makes a major contribution to disease chronicity. Transforming growth factor-b is a potent profibrogenic factor whose expression is increased in the asthmatic airways and is a prime candidate for the initiation and persistence of airway remodelling in asthma.This review highlights the role of transforming growth factor-b in the asthmatic lung, incorporating biosynthesis, signalling pathways and functional outcome. In vivo, however, it is the balance between transforming growth factor-b and other growth factors, such as epidermal growth factor, which will determine the extent of fibrosis in the airways.A fuller comprehension of the actions of transforming growth factor-b, and its interaction with other signalling pathways, such as the epidermal growth factor receptor signalling cascade, may enable development of therapies that control airway remodelling where there is an unmet clinical need.

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“…Similarly, Wyatt et al demonstrated that bronchial epithelial cells migrate in response to porcine RLN in a wounding assay. 24 Thus, local production of RLN by tumor cells or stromal cells may play a role in enhancing migration. RLN also led to increased invasiveness of both HEC-1B and KLE cells through an artificial basement membrane.…”

Section: Discussionmentioning

confidence: 99%

The role of relaxin in endometrial cancer

Kamat¹,

Feng²,

Agoulnik³

et al. 2006

Cancer Biology & Therapy

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Relaxin Stimulates Bronchial Epithelial Cell PKA Activation, Migration, and Ciliary Beating¹

Cited by 24 publications

References 41 publications

Relaxin Enhances the Oncogenic Potential of Human Thyroid Carcinoma Cells

Relaxin Enhances the Oncogenic Potential of Human Thyroid Carcinoma Cells

The contribution of transforming growth factor- and epidermal growth factor signalling to airway remodelling in chronic asthma

The role of relaxin in endometrial cancer

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Relaxin Stimulates Bronchial Epithelial Cell PKA Activation, Migration, and Ciliary Beating1

Cited by 24 publications

References 41 publications

Relaxin Enhances the Oncogenic Potential of Human Thyroid Carcinoma Cells

Relaxin Enhances the Oncogenic Potential of Human Thyroid Carcinoma Cells

The contribution of transforming growth factor- and epidermal growth factor signalling to airway remodelling in chronic asthma

The role of relaxin in endometrial cancer

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Product

Resources

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Relaxin Stimulates Bronchial Epithelial Cell PKA Activation, Migration, and Ciliary Beating¹