Role of relaxin-2 in human primary osteosarcoma

Ma, Jinfeng; Niu, Min; Yang, Wenjiu; Zang, Lei; Xi, Yongming

doi:10.1186/1475-2867-13-59

Cited by 22 publications

(15 citation statements)

References 24 publications

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“…To date, H2 relaxin has been implicated in the progression and invasiveness of a variety of cancers, including breast, thyroid and ovarian/endometrial cancers . Some recent preliminary evidence suggests a role for relaxin in the cancers of the liver, bone, uterus and esophagus . One study showed that H2 relaxin transcript expression was present in all neoplastic breast tissues compared with only 3 out of 8 normal tissues .…”

Section: Other Reproductive Tissue‐based Cancersmentioning

confidence: 99%

Targeting the relaxin hormonal pathway in prostate cancer

Neschadim¹,

Summerlee

Silvertown³

2014

Intl Journal of Cancer

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Targeting the androgen signalling pathway has long been the hallmark of anti-hormonal therapy for prostate cancer. However, development of androgen-independent prostate cancer is an inevitable outcome to therapies targeting this pathway, in part, owing to the shift from cancer dependence on androgen signalling for growth in favor of augmentation of other cellular pathways that provide proliferation-, survival-and angiogenesis-promoting signals. This review focuses on the role of the hormone relaxin in the development and progression of prostate cancer, prior to and after the onset of androgen independence, as well as its role in cancers of other reproductive tissues. As the body of literature expands, examining relaxin expression in cancerous tissues and its role in a growing number of in vitro and in vivo cancer models, our understanding of the important involvement of this hormone in cancer biology is becoming clearer. Specifically, the pleiotropic functions of relaxin affecting cell growth, angiogenesis, blood flow, cell migration and extracellular matrix remodeling are examined in the context of cancer progression. The interactions and intercepts of the intracellular signalling pathways of relaxin with the androgen pathway are explored in the context of progression of castration-resistant and androgen-independent prostate cancers. We provide an overview of current anti-hormonal therapeutic treatment options for prostate cancer and delve into therapeutic approaches and development of agents aimed at specifically antagonizing relaxin signalling to curb tumor growth. We also discuss the rationale and challenges utilizing such agents as novel anti-hormonals in the clinic, and their potential to supplement current therapeutic modalities.Steroidal sex hormones-estrogens, androgens and progestogens-have all been implicated in the progression of cancers of different hormone-sensitive tissues.

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Section: Other Reproductive Tissue‐based Cancersmentioning

confidence: 99%

Targeting the relaxin hormonal pathway in prostate cancer

Neschadim¹,

Summerlee

Silvertown³

2014

Intl Journal of Cancer

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“…Human soft tissue sarcomas usually develop first in an extra thoracic location but have an increased propensity to metastasize to the lung. It has been noted that extra-thoracic tumors send out pilot cells that could attach to the pulmonary endothelium and could in theory alter regional lung mechanics by either stiffening the lung tissue or by increasing fluid and inflammatory cell accumulation near the pilot cell attachment in the endothelium producing changes in lung compliance [ 1 – 8 ]. We hypothesized in this study that prior to the computed tomographic-based (CT) visualization of a metastatic lung nodule, CT measures of regional lung mechanics [ 9 – 21 ] could detect changes in lung compliance not visible to the human eye on standard chest CT examinations and that these changes in compliance would precede the development of metastatic lung nodules that are subsequently visible on CT.…”

Section: Introductionmentioning

confidence: 99%

Quantitative computed tomography determined regional lung mechanics in normal nonsmokers, normal smokers and metastatic sarcoma subjects

et al. 2017

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ObjectivesExtra-thoracic tumors send out pilot cells that attach to the pulmonary endothelium. We hypothesized that this could alter regional lung mechanics (tissue stiffening or accumulation of fluid and inflammatory cells) through interactions with host cells. We explored this with serial inspiratory computed tomography (CT) and image matching to assess regional changes in lung expansion.Materials and methodsWe retrospectively assessed 44 pairs of two serial CT scans on 21 sarcoma patients: 12 without lung metastases and 9 with lung metastases. For each subject, two or more serial inspiratory clinically-derived CT scans were retrospectively collected. Two research-derived control groups were included: 7 normal nonsmokers and 12 asymptomatic smokers with two inspiratory scans taken the same day or one year apart respectively. We performed image registration for local-to-local matching scans to baseline, and derived local expansion and density changes at an acinar scale. Welch two sample t test was used for comparison between groups. Statistical significance was determined with a p value < 0.05.ResultsLung regions of metastatic sarcoma patients (but not the normal control group) demonstrated an increased proportion of normalized lung expansion between the first and second CT. These hyper-expanded regions were associated with, but not limited to, visible metastatic lung lesions. Compared with the normal control group, the percent of increased normalized hyper-expanded lung in sarcoma subjects was significantly increased (p < 0.05). There was also evidence of increased lung “tissue” volume (non-air components) in the hyper-expanded regions of the cancer subjects relative to non-hyper-expanded regions. “Tissue” volume increase was present in the hyper-expanded regions of metastatic and non-metastatic sarcoma subjects. This putatively could represent regional inflammation related to the presence of tumor pilot cell-host related interactions.ConclusionsThis new quantitative CT (QCT) method for linking serial acquired inspiratory CT images may provide a diagnostic and prognostic means to objectively characterize regional responses in the lung following oncological treatment and monitoring for lung metastases.

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“…Signaling by relaxin-2 through its target receptors enhances the growth of pubic ligaments and ripening of the cervix during birth. Several groups, including ours, have demonstrated that H2 relaxin plays a role in OS carcinogenesis [ 3 ]. However, the mechanism that RLN2 functions in detail is not clear.…”

Section: Introductionmentioning

confidence: 99%

“…It has recently been found that chemically synthesized AT-001, an analog of human RLN2, could suppress PC3 xenograft growth and sensitize PC3 xenografts to docetaxel, standard first-line chemotherapy for HRPC [ 28 ]. We have previously found the levels of RLN2 mRNA expression in OS tissue samples were significantly higher than those in the corresponding nontumor tissue samples [ 3 ]. Whether RLN2 could be important therapeutic targets for overcoming chemoresistance or whether RLN2 overcomes chemoresistance by AKT/NF- κ B pathway is not very clear to date.…”

Section: Introductionmentioning

confidence: 99%

RLN2 Is a Positive Regulator of AKT-2-Induced Gene Expression Required for Osteosarcoma Cells Invasion and Chemoresistance

Huang

Han

et al. 2015

BioMed Research International

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The aim of the study was to determine the effect of H2 relaxin (RLN2) on invasion, migration, and chemosensitivity to cisplatin in human osteosarcoma U2-OS and MG-63 cells and then to investigate the effect of RLN2 on the AKT/NF-κB signaling pathway. The expression of RLN2, p-AKT (Ser473), and p-ERK1/2 (Phospho-Thr202/Tyr204) proteins was detected by western blot in OS tissues from 21 patients with pulmonary metastatic disease, and the correlation between RLN2 and p-AKT or RLN2 and p-ERK1/2 expression was investigated. RLN2 expression was inhibited by RLN2 siRNA transfection in the MG-63 cells. RLN2 was overexpressed in the U2-OS cells by treatment with recombinant relaxin. The results showed that positive relation was found between RLN2 and p-AKT expression in tissues of OS. Silencing RLN2 inhibited cell migratory and invasive ability and angiogenesis formation and increased the chemosensitivity to cisplatin in MG-63 cells. RLN2 overexpression promoted migratory and invasive ability and angiogenesis and increased the chemoresistance to cisplatin in U2-OS cells. Silencing RLN2 inhibited the activity of AKT/NF-κB signaling pathway in MG-63 cells, and vice versa. Blockage of both pathways by specific inhibitors abrogated RLN2-induced survival and invasion of OS cells, and vice versa. Our results indicated RLN2 confers to migratory and invasive ability, angiogenesis, and chemoresistance to cisplatin via modulating the AKT/NF-κB signaling pathway in vitro.

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Role of relaxin-2 in human primary osteosarcoma

Cited by 22 publications

References 24 publications

Targeting the relaxin hormonal pathway in prostate cancer

Targeting the relaxin hormonal pathway in prostate cancer

Quantitative computed tomography determined regional lung mechanics in normal nonsmokers, normal smokers and metastatic sarcoma subjects

RLN2 Is a Positive Regulator of AKT-2-Induced Gene Expression Required for Osteosarcoma Cells Invasion and Chemoresistance

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