Recombinant H2 relaxin inhibits apoptosis and induces cell proliferation in cultured leiomyoma cells without affecting those in cultured normal myometrial cells

Suzuki, Kaho; Nakabayashi, Koji; Yamada, Ai; Lodhi, Romana Sz.; Hazama, Rhoichi; Ebina, Yasuhiko; Yamada, Hideto

doi:10.1016/j.fertnstert.2011.12.011

Cited by 11 publications

(12 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…tissue invasion, and tumour angiogenesis [3][4][5], and inhibiting apoptosis [6]. RLN2-mediated RXFP1 activation contributes to tissue invasion and metastasis of tumour cells in several ways.…”

Section: No Conflicts Of Interest Were Declaredmentioning

confidence: 99%

“…The heterodimeric peptide hormone relaxin binds to the G‐protein‐coupled receptor RXFP1 and is up‐regulated in cancer . The main human relaxin isoform, RLN2, can promote tumour progression in a tumour‐specific context by enhancing tumour cell proliferation, tissue invasion, and tumour angiogenesis , and inhibiting apoptosis . RLN2‐mediated RXFP1 activation contributes to tissue invasion and metastasis of tumour cells in several ways.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

C1q‐tumour necrosis factor‐related protein 8 (CTRP8) is a novel interaction partner of relaxin receptor RXFP1 in human brain cancer cells

Głogowska

Kunanuvat

Stetefeld

et al. 2013

The Journal of Pathology

View full text Add to dashboard Cite

We report a novel ligand-receptor system composed of the leucine-rich G-protein-coupled relaxin receptor, RXFP1, and the C1q-tumour necrosis factor-related protein 8 (CTRP8) in human primary brain cancer, a tumour entity devoid of the classical RXFP1 ligands, RLN1-3. In structural homology studies and computational docking experiments we delineated the N-terminal region of the globular C1q region of CTRP8 and the leucine-rich repeat units 7 and 8 of RXFP1 to mediate this new ligand-receptor interaction. CTRP8 secreted from HEK293T cells, recombinant human (rh) CTRP8, and short synthetic peptides derived from the C1q globular domain of human CTRP8 caused the activation of RXFP1 as determined by elevated intracellular cAMP levels and the induction of a marked pro-migratory phenotype in established glioblastoma (GB) cell lines and primary cells from GB patients. Employing a small competitor peptide, we were able to disrupt the CTRP8-RXFP1-induced increased GB motility. The CTRP8-RXFP1-mediated migration in GB cells involves the activation of PI3K and specific protein kinase C pathways and the increased production/secretion of the potent lysosomal protease cathepsin B (cathB), a known prognostic marker of GB. Specific inhibition of CTRP8-induced cathB activity effectively blocked the ability of primary GB to invade laminin matrices. Finally, co-immunoprecipitation studies revealed the direct interaction of human CTRP8 with RXFP1. Our results support a therapeutic approach in GB aimed at targeting multiple steps of the CTRP8-RXFP1 signalling pathway by a combined inhibitor and peptide-based strategy to block GB dissemination within the brain.

show abstract

Section: No Conflicts Of Interest Were Declaredmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

C1q‐tumour necrosis factor‐related protein 8 (CTRP8) is a novel interaction partner of relaxin receptor RXFP1 in human brain cancer cells

Głogowska

Kunanuvat

Stetefeld

et al. 2013

The Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…Mediator subcomplex 12 is a protein involved in the organisation of the transcription machinery showing a high degree of evolutionary conservation among mammalian species in particular in the region encoded by the UL-hotspot region [8]. While UL-derived cell cultures are a wide-spread model system for research into the pathogenesis and behavior of the tumors [2, 9–11] recent results challenge the usefulness of this model for the group of tumors carrying MED12 mutations. Contrary to the expectations a rapid loss of mutated cells accompanied in vitro growth of UL-derived cell cultures [12].…”

Section: Introductionmentioning

confidence: 99%

Factors affecting the loss of MED12-mutated leiomyoma cells during in vitro growth

et al. 2017

View full text Add to dashboard Cite

Uterine leiomyomas (UL) are the most prevalent symptomatic human tumors at all and somatic mutations of the gene encoding mediator subcomplex 12 (MED12) constitute the most frequent driver mutations in UL. Recently, a rapid loss of mutated cells during in vitro growth of UL-derived cell cultures was reported, resulting in doubts about the benefits of UL-derived cell cultures. To evaluate if the rapid loss of MED12-mutated cells in UL cell cultures depends on in vitro passaging, we set up cell cultures from nine UL from 40–50 year old Caucasian patients with at least one UL. Cultured UL cells were investigated for loss of MED12-mutated cells. Genetic characterization of native tumor samples and adjacent myometrium was done by array analysis. “Aged” primary cultures without passaging were compared to cells of three subsequent passages. Comparative analyses of the mutated/non-mutated ratios between native tissue, primary cells, and cultured tumor cells revealed a clear decrease of MED12-mutated cells. None of the tumors showed gross alterations of the array profiles, excluding the presence of gross genomic imbalances besides the MED12 mutations as a reason for the intertumoral variation in the loss of MED12-mutated cells. Albeit at a lesser rate, loss of MED12-mutated cells from cell cultures of UL occurs even without passaging thus indicating the requirement of soluble factors or matrix components lacking in vitro. Identification of these factors can help to understand the mechanisms of the growth of the most frequent type of uterine leiomyomas and to decipher novel drug targets.

show abstract

“…In human osteosarcoma cells, relaxin promotes faster in vitro growth, invasion, and angiogenesis via the Akt and VEGF pathways, and small interfering RNA-mediated knockdown of relaxin greatly mitigates these effects (Ma et al, 2013a,b). The peptide hastens the proliferation of human leiomyoma cells (Suzuki et al, 2012). A clinical study in 108 patients with hepatocellular carcinoma identified expression of relaxin in tumor tissue as an independent predictor of poor prognosis (Pan et al, 2013).…”

mentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. XCV. Recent Advances in the Understanding of the Pharmacology and Biological Roles of Relaxin Family Peptide Receptors 1–4, the Receptors for Relaxin Family Peptides

Halls¹,

Bathgate²,

Sutton³

et al. 2015

Pharmacol Rev

118

View full text Add to dashboard Cite

Recombinant H2 relaxin inhibits apoptosis and induces cell proliferation in cultured leiomyoma cells without affecting those in cultured normal myometrial cells

Cited by 11 publications

References 31 publications

C1q‐tumour necrosis factor‐related protein 8 (CTRP8) is a novel interaction partner of relaxin receptor RXFP1 in human brain cancer cells

C1q‐tumour necrosis factor‐related protein 8 (CTRP8) is a novel interaction partner of relaxin receptor RXFP1 in human brain cancer cells

Factors affecting the loss of MED12-mutated leiomyoma cells during in vitro growth

International Union of Basic and Clinical Pharmacology. XCV. Recent Advances in the Understanding of the Pharmacology and Biological Roles of Relaxin Family Peptide Receptors 1–4, the Receptors for Relaxin Family Peptides

Contact Info

Product

Resources

About