BACKGROUND/AIMHyaluronic acid (HA) is a large glycosaminoglycan composed of an extracellular matrix. The HA-rich microenvironment and receptors of HA have been suggested to play roles in cancer progression. The biological and clinical significance of receptor for HA-mediated motility (RHAMM), known as CD168 in prostate cancer (PC) remains unknown. This study aimed to investigate the expression of RHAMM, as well as its functional and clinical relevance in PC.MATERIALS AND METHODSHA concentration and RHAMM mRNA expression were examined in 3 PC cell lines (LNCaP, PC3 and DU145). We investigated the effect of HA and RHAMM on the migratory ability of PC cells using a transwell migration assay. Immunohistochemistry was also used to evaluate the RHAMM expression pattern in pre-treatment tissue samples from 99 patients with metastatic hormone-sensitive PC (HSPC) who received androgen deprivation therapy (ADT).RESULTSHA was secreted in all cultured PC cell lines. Among the total HA, low-molecular-weight HA (LMW-HA) (<100 kDa) was detected all examined cell lines. The number of migration cells was significantly increased by adding LMW-HA. RHAMM mRNA expression was increased in DU145 cells. Knockdown of RHAMM using small-interfering RNA resulted in decreased cell migration. Immunohistochemical analysis revealed strong RHAMM expression in 31 (31.3%) patients with metastatic HSPC. A strong RHAMM expression was significantly associated with short ADT duration and poor survival in univariate and multivariate analyses.CONCLUSIONThe size of HA is important in terms of PC progression. LMW-HA and RHAMM enhanced PC cell migration. RHAMM could be used as a novel prognostic marker in patients with metastatic HSPC.

2021-06-01·Journal of Investigative Dermatology1区 · 医学

Function-Blocking RHAMM Peptides Attenuate Fibrosis and Promote Antifibrotic Adipokines in a Bleomycin-Induced Murine Model of Systemic Sclerosis

1区 · 医学

Article

作者: Wu, Kitty Yuechuan ; Yazdani, Arjang ; Turley, Eva A ; Sabino, Alexis ; Minkhorst, Kathryn ; Kim, Stephanie ; Liu, Violet Muhan

Systemic sclerosis a chronic, fibrotic disorder associated with high disease-specific mortality and morbidity. Cutaneous manifestations include dermal thickening and obliteration of dermal adipose tissue. Accumulation of low-molecular-weight hyaluronan, which signals through the receptor for hyaluronan-mediated motility, RHAMM, leads to progressive fibrosis and is correlated with increased severity of systemic sclerosis. The purpose of this study is to test the efficacy of two function-blocking RHAMM peptides, NPI-110 and NPI-106, in reducing skin fibrosis in a bleomycin-induced mouse model of systemic sclerosis. NPI-110 reduced visible measures of fibrosis (dermal thickness and collagen production, deposition, and organization) and profibrotic gene expression (Tgfb1, c-Myc, Col1a1, Col3a1). NPI-110 treatment also increased the expression of the antifibrotic adipokines perilipin and adiponectin. Both RHAMM peptides strongly reduced dermal RHAMM expression, predicting that dermal fibroblasts are peptide targets. Transcriptome and cell culture analyses using Rhamm-/- and Rhamm-rescued dermal fibroblasts reveal a TGFβ1/RHAMM/MYC signaling axis that promotes fibrogenic gene expression and myofibroblast differentiation. RHAMM function‒blocking peptides suppress this signaling and prevent TGFβ1-induced myofibroblast differentiation. These results suggest that inhibiting RHAMM signaling will offer a treatment method for cutaneous fibrosis in systemic sclerosis.

2021-04-01·Pain1区 · 医学

Sexual dimorphism in the nociceptive effects of hyaluronan

1区 · 医学

Article

作者: Green, Paul G. ; Bonet, Ivan J.M. ; Levine, Jon D.

AbstractIntradermal administration of low-molecular-weight hyaluronan (LMWH) in the hind paw induced dose-dependent (0.1, 1, or 10 µg) mechanical hyperalgesia of similar magnitude in male and female rats. However, the duration of LMWH hyperalgesia was greater in females. This sexual dimorphism was eliminated by bilateral ovariectomy and by intrathecal administration of an oligodeoxynucleotide (ODN) antisense to the G-protein-coupled estrogen receptor (GPR30) mRNA in females, indicating estrogen dependence. To assess the receptors at which LMWH acts to induce hyperalgesia, LMWH was administered to groups of male and female rats that had been pretreated with ODN antisense (or mismatch) to the mRNA for 1 of 3 hyaluronan receptors, cluster of differentiation 44 (CD44), toll-like receptor 4, or receptor for hyaluronan-mediated motility (RHAMM). Although LMWH-induced hyperalgesia was attenuated in both male and female rats pretreated with ODN antisense for CD44 and toll-like receptor 4 mRNA, RHAMM antisense pretreatment only attenuated LMWH-induced hyperalgesia in males. Oligodeoxynucleotide antisense for RHAMM, however, attenuated LMWH-induced hyperalgesia in female rats treated with ODN antisense to GPR30, as well as in ovariectomized females. Low-molecular-weight hyaluronan–induced hyperalgesia was significantly attenuated by pretreatment with high-molecular-weight hyaluronan (HMWH) in male, but not in female rats. After gonadectomy or treatment with ODN antisense to GPR30 expression in females, HMWH produced similar attenuation of LMWH-induced hyperalgesia to that seen in males. These experiments identify nociceptors at which LMWH acts to produce mechanical hyperalgesia, establishes estrogen dependence in the role of RHAMM in female rats, and establishes estrogen dependence in the inhibition of LMWH-induced hyperalgesia by HMWH.

100 项与 RHAMM-R3 peptide vaccine(Memorial Sloan-Kettering Cancer Center) 相关的药物交易

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