RHAMM Is a Multifunctional Protein That Regulates Cancer Progression

Messam, Britney Jodi-Ann; Tölg, Cornelia; McCarthy, James B.; Nelson, Andrew C.; Turley, Eva A.

doi:10.3390/ijms221910313

Cited by 28 publications

(37 citation statements)

References 131 publications

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“…HMMR is a multifunctional protein that regulates cancer progression. Elevated HMMR expression is a feature of most cancers and is also an indicator of poor prognosis in many cancers (15). In addition, its ability to promote inflammation and fibrosis exacerbates the progression of cancer (16,17).…”

Section: Discussionmentioning

confidence: 99%

Identifying a lactic acid metabolism-related gene signature contributes to predicting prognosis, immunotherapy efficacy, and tumor microenvironment of lung adenocarcinoma

Zhao¹,

Wang²,

Li³

et al. 2022

Front. Immunol.

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Lactic acid, once considered as an endpoint or a waste metabolite of glycolysis, has emerged as a major regulator of cancer development, maintenance, and progression. However, studies about lactic acid metabolism-related genes (LRGs) in lung adenocarcinoma (LUAD) remain unclear. Two distinct molecular subtypes were identified on basis of 24 LRGs and found the significant enrichment of subtype A in metabolism-related pathways and had better overall survival (OS). Subsequently, a prognostic signature based on 5 OS-related LRGs was generated using Lasso Cox hazards regression analysis in TCGA dataset and was validated in two external cohorts. Then, a highly accurate nomogram was cosntructed to improve the clinical application of the LRG_score. By further analyzing the LRG_score, higher immune score and lower stromal score were found in the low LRG_score group, which presented a better prognosis. Patients with low LRG_score also exhibited lower somatic mutation rate, tumor mutation burden (TMB), and cancer stem cell (CSC) index. Three more independent cohorts (GSE126044: anti-PD-1, GSE135222: anti-PD-1, and IMvigor210: anti-PD-L1) were analyzed, and the results showed that patients in the low LRG_score category were more responsive to anti-PD-1/PD-L1 medication and had longer survival times. It was also determined that gefitinib, etoposide, erlotinib, and gemcitabine were more sensitive to the low LRG_score group. Finally, we validated the stability and reliability of LRG_score in cell lines, clinical tissue samples and HPA databases. Overall, the LRG_score may improve prognostic information and provide directions for current research on drug treatment strategies for LUAD patients.

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Section: Discussionmentioning

confidence: 99%

Identifying a lactic acid metabolism-related gene signature contributes to predicting prognosis, immunotherapy efficacy, and tumor microenvironment of lung adenocarcinoma

Zhao¹,

Wang²,

Li³

et al. 2022

Front. Immunol.

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“…RHAMM is a multifunctional protein that controls differential response to injury contexts (28). Normal prostatic tissue dose not express RHAMM (19).…”

Section: Discussionmentioning

confidence: 99%

Receptor for Hyaluronic Acid-mediated Motility (RHAMM) Is Associated With Prostate Cancer Migration and Poor Prognosis

Minato

Kudo

Noguchi

et al. 2023

Cancer Genomics Proteomics

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Background/Aim: Hyaluronic 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 Methods: HA 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). Results: HA was secreted in all cultured PC cell lines. Among the total HA, lowmolecular-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. Conclusion: The 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.Androgen deprivation therapy (ADT) is a gold-standard treatment for patients with metastatic prostate cancer (PC). Metastatic hormone-sensitive PC (HSPC) progresses to castration-resistant PC (CRPC) despite a favorable initial ADT response. Recently, guidelines recommended a combination of abiraterone, apalutamide, or enzalutamide with ADT as firstline therapy for patients with metastatic HSPC (1, 2). However, a large retrospective study using real-world data in the United States revealed that approximately 43% of patients received ADT alone as first-line therapy for metastatic HSPC (3). Additionally, we previously demonstrated that some patients with metastatic HSPC achieved long-term survival under ADT alone (4). Therefore, biomarkers to effectively predict primary ADT response are required.The microenvironment surrounding the tumor cells plays an important role in cancer progression. Hyaluronic acid (HA) is a large glycosaminoglycan composed of an extracellular matrix. A previous study revealed that HA-rich stroma promotes tumor progression in various cancer cells (5-7). HA was detected relatively frequently and abundantly 203

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“…It is important to put our gene expression data in the context of this presented functional data, because Gene expression studies are limited to proteins that have steady state concentrations of mRNA. This excludes proteins mainly regulated at the post-translational level, such as the protein RHAMM 44 . Taken together with the previous observations indicated above, our findings, the possibility that Hyaluronan synthase 2 can control the spread of Infantile fibrosarcoma.…”

Section: Discussionmentioning

confidence: 99%

Hyaluronan nanoscale clustering and Hyaluronan synthase 2 expression are linked to the invasion of child fibroblasts and infantile fibrosarcoma in vitro and in vivo

Tonge

Dunning

López-Guajardo

et al. 2022

Sci Rep

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Infantile fibrosarcoma is a rare childhood tumour that originates in the fibrous connective tissue of the long bones for which there is an urgent need to identify novel therapeutic targets. This study aims to clarify the role of the extracellular matrix component hyaluronan in the invasion of child fibroblasts and Infantile fibrosarcoma into the surrounding environment. Using nanoscale super-resolution STED (Stimulated emission depletion) microscopy followed by computational image analysis, we observed, for the first time, that invasive child fibroblasts showed increased nanoscale clustering of hyaluronan at the cell periphery, as compared to control cells. Hyaluronan was not observed within focal adhesions. Bioinformatic analyses further revealed that the increased nanoscale hyaluronan clustering was accompanied by increased gene expression of Hyaluronan synthase 2, reduced expression of Hyaluronidase 2 and CD44, and no change of Hyaluronan synthase 1 and Hyaluronidases 1, 3, 4 or 5. We further observed that the expression of the Hyaluronan synthase 1, 2 and 3, and the Hyaluronidase 3 and 5 genes was linked to reduced life expectancy of fibrosarcoma patients. The invasive front of infantile fibrosarcoma tumours further showed increased levels of hyaluronan, as compared to the tumour centre. Taken together, our findings are consistent with the possibility that while Hyaluronan synthase 2 increases the levels, the Hyaluronidases 3 and 5 reduce the weight of hyaluronan, resulting in the nanoscale clustering of hyaluronan at the leading edge of cells, cell invasion and the spread of Infantile fibrosarcoma.

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RHAMM Is a Multifunctional Protein That Regulates Cancer Progression

Cited by 28 publications

References 131 publications

Identifying a lactic acid metabolism-related gene signature contributes to predicting prognosis, immunotherapy efficacy, and tumor microenvironment of lung adenocarcinoma

Identifying a lactic acid metabolism-related gene signature contributes to predicting prognosis, immunotherapy efficacy, and tumor microenvironment of lung adenocarcinoma

Receptor for Hyaluronic Acid-mediated Motility (RHAMM) Is Associated With Prostate Cancer Migration and Poor Prognosis

Hyaluronan nanoscale clustering and Hyaluronan synthase 2 expression are linked to the invasion of child fibroblasts and infantile fibrosarcoma in vitro and in vivo

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