scholarly journals The Roadmap of RANKL/RANK Pathway in Cancer

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1978
Author(s):  
Sandra Casimiro ◽  
Guilherme Vilhais ◽  
Inês Gomes ◽  
Luis Costa
Keyword(s):  
Cancer Biology ◽  
Immune Modulation ◽  
Clinical Evidence ◽  
Standard Of Care ◽  
Nuclear Factor Κb ◽  
Phenotypic Traits ◽  
Immune Mediator ◽  
New Era ◽  
Receptor Activator ◽  
Rank Signaling

The receptor activator of the nuclear factor-κB ligand (RANKL)/RANK signaling pathway was identified in the late 1990s and is the key mediator of bone remodeling. Targeting RANKL with the antibody denosumab is part of the standard of care for bone loss diseases, including bone metastases (BM). Over the last decade, evidence has implicated RANKL/RANK pathway in hormone and HER2-driven breast carcinogenesis and in the acquisition of molecular and phenotypic traits associated with breast cancer (BCa) aggressiveness and poor prognosis. This marked a new era in the research of the therapeutic use of RANKL inhibition in BCa. RANKL/RANK pathway is also an important immune mediator, with anti-RANKL therapy recently linked to improved response to immunotherapy in melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC). This review summarizes and discusses the pre-clinical and clinical evidence of the relevance of the RANKL/RANK pathway in cancer biology and therapeutics, focusing on bone metastatic disease, BCa onset and progression, and immune modulation.

scholarly journals The Intrinsic and Extrinsic Implications of RANKL/RANK Signaling in Osteosarcoma: From Tumor Initiation to Lung Metastases

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 398 ◽  
Author(s):  
Benjamin Navet ◽  
Kosei Ando ◽  
Jorge Vargas-Franco ◽  
Régis Brion ◽  
Jérome Amiaud ◽  
...  
Keyword(s):  
Lung Metastases ◽  
Nuclear Factor Κb ◽  
Osteosarcoma Cell ◽  
Nuclear Factor ◽  
Osteosarcoma Cells ◽  
Cellular Processes ◽  
Receptor Activator ◽  
Rank Signaling

Background: Osteosarcoma is the most frequent form of malignant pediatric bone tumor. Despite the current therapeutic arsenal, patient life-expectancy remains low if metastases are detected at the time of diagnosis, justifying research into better knowledge at all stages of osteosarcoma ontogenesis and identification of new therapeutic targets. Receptor Activator of Nuclear factor κB (RANK)expression has been reported in osteosarcoma cells, raising the question of Receptor Activator of Nuclear factor κB Ligand (RANKL)/RANK signaling implications in these tumor cells (intrinsic), in addition to previously reported implications through osteoclast activation in the tumor microenvironment (extrinsic). Methods: Based on in vitro and in vivo experimentations using human and mouse osteosarcoma cell lines, the consequences on the main cellular processes of RANK expression in osteosarcoma cells were analyzed. Results: The results revealed that RANK expression had no impact on cell proliferation and tumor growth, but stimulated cellular differentiation and, in an immune-compromised environment, increased the number of lung metastases. The analysis of RANKL, RANK and osteoprotegerin (OPG) expressions in biopsies of a cohort of patients revealed that while RANK expression in osteosarcoma cells was not significantly different between patients with or without metastases at the time of diagnosis, the OPG/RANK ratio decreased significantly. Conclusion: Altogether, these results are in favor of RANKL-RANK signaling inhibition as an adjuvant for the treatment of osteosarcoma.

Acanthopanax senticosus aqueous extract ameliorates ovariectomy-induced bone loss in middle-aged mice by inhibiting the receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis

2020 ◽  
Vol 11 (11) ◽  
pp. 9696-9709
Author(s):  
Huanhuan Xu ◽  
Jing Xu ◽  
Fei Chen ◽  
Titi Liu ◽  
Jin Li ◽  
...  
Keyword(s):  
Bone Loss ◽  
Signaling Pathways ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Middle Aged ◽  
Acanthopanax Senticosus ◽  
Treatment Of Osteoporosis ◽  
Aged Mice ◽  
Receptor Activator ◽  
Rank Signaling

ASAE ameliorates ovariectomy-induced bone loss in middle-aged mice by inhibiting RANKL-induced osteoclastogenesis through suppression of RANK signaling pathways and could be potentially used in mediated treatment of osteoporosis.

Opiophobia in Cancer Biology- Justified? - The Role of Perioperative Use of Opioids in Cancer Recurrence

2019 ◽  
Vol 25 (28) ◽  
pp. 3020-3027 ◽  
Author(s):  
Mir W. Sekandarzad ◽  
Chris Doornebal ◽  
Markus W. Hollmann
Keyword(s):  
Pain Management ◽  
Cancer Biology ◽  
Tumor Biology ◽  
Cancer Recurrence ◽  
Standard Of Care ◽  
Cancer Surgery ◽  
Perioperative Pain Management ◽  
Tumor Growth And Metastasis

: Opioids remain the standard of care in the provision of analgesia in the patient undergoing cancer surgery preoperatively. : The effects of opioids on tumor growth and metastasis have been discussed for many years. In recent years their use as part of the perioperative pain management bundle in the patients undergoing cancer surgery has been thought to promote cancer recurrence and metastasis. : This narrative review highlights earlier and more recent in vitro, in vivo and human retrospective studies that yield conflicting results as to the immune-modulatory effects of morphine on tumor biology. The article examines and explains the discrepancies with regards to the seemingly opposite results of morphine in the tumor milieu. The results of both, earlier studies that demonstrated procarcinogenic effects versus the data of more recent refined rodent studies that yielded neutral or even anti-carcinogenic effects are presented here. : Until the results of prospective randomized controlled trials are available to clarify this important question, it is currently not warranted to support opiophobia and opioids continue to constitute a pivotal role in the pain management of cancer patients.

Opg, Rank, and Rankl in Tooth Development: Co-ordination of Odontogenesis and Osteogenesis

2004 ◽  
Vol 83 (3) ◽  
pp. 241-244 ◽  
Author(s):  
A. Ohazama ◽  
J.-M. Courtney ◽  
P.T. Sharpe
Keyword(s):  
Tooth Development ◽  
Nuclear Factor Κb ◽  
Cellular Interactions ◽  
Rankl Expression ◽  
Dental Papilla ◽  
Spatiotemporal Expression ◽  
Receptor Activator ◽  
Explant Cultures ◽  
Enamel Epithelium ◽  
Tooth Germs

Osteoprotegerin (OPG), receptor activator of nuclear factor-κB (RANK), and RANK ligand (RANKL) are mediators of various cellular interactions, including bone metabolism. We analyzed expression of these three genes during murine odontogenesis from epithelial thickening to cytodifferentiation stages. Opg showed expression in the thickening and bud epithelium. Expression of Opg and Rank was observed in both the internal and the external enamel epithelium as well as in the dental papilla mesenchyme. Although Rankl expression was not detected in tooth epithelium or mesenchyme, it was expressed in pre-osteogenic mesenchymal cells close to developing tooth germs. All three genes were detected in developing dentary bone at P0. The addition of exogenous OPG to explant cultures of tooth primordia produced a delay in tooth development that resulted in reduced mineralization. We propose that the spatiotemporal expression of these molecules in early tooth and bone primordia cells has a role in co-ordinating bone and tooth development.

scholarly journals Receptor activator of nuclear factor-κB ligand and osteoprotegerin

Cancer ◽  
2001 ◽  
Vol 92 (3) ◽  
pp. 460-470 ◽  
Author(s):  
Lorenz C. Hofbauer ◽  
Andreas Neubauer ◽  
Armin E. Heufelder
Keyword(s):  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Receptor Activator

scholarly journals Porphyromonas gingivalis Infection-Associated Periodontal Bone Resorption Is Dependent on Receptor Activator of NF-κB Ligand

2013 ◽  
Vol 81 (5) ◽  
pp. 1502-1509 ◽  
Author(s):  
Xiaozhe Han ◽  
Xiaoping Lin ◽  
Xiaoqian Yu ◽  
Jiang Lin ◽  
Toshihisa Kawai ◽  
...  
Keyword(s):  
B Cells ◽  
Bone Resorption ◽  
Fusion Protein ◽  
Porphyromonas Gingivalis ◽  
Nuclear Factor Κb ◽  
Infected Group ◽  
T And B Cells ◽  
Content Type ◽  
Receptor Activator ◽  
Control Fusion

ABSTRACTPorphyromonas gingivalisis one of the oral microorganisms associated with human chronic periodontitis. The purpose of this study is to determine the role of the receptor activator of nuclear factor-κB ligand (RANKL) inP. gingivalisinfection-associated periodontal bone resorption. Inbred female Rowett rats were infected orally on four consecutive days (days 0 to 3) with 1 × 109P. gingivalisbacteria (strain ATCC 33277). Separate groups of rats also received an injection of anti-RANKL antibody, osteoprotegerin fusion protein (OPG-Fc), or a control fusion protein (L6-Fc) into gingival papillae in addition toP. gingivalisinfection. Robust serum IgG and salivary IgA antibody (P< 0.01) and T cell proliferation (P< 0.05) responses toP. gingivaliswere detected at day 7 and peaked at day 28 inP. gingivalis-infected rats. Both the concentration of soluble RANKL (sRANKL) in rat gingival tissues (P< 0.01) and periodontal bone resorption (P< 0.05) were significantly elevated at day 28 in theP. gingivalis-infected group compared to levels in the uninfected group. Correspondingly, RANKL-expressing T and B cells in rat gingival tissues were significantly increased at day 28 in theP. gingivalis-infected group compared to the levels in the uninfected group (P< 0.01). Injection of anti-RANKL antibody (P< 0.05) or OPG-Fc (P< 0.01), but not L6-Fc, into rat gingival papillae afterP. gingivalisinfection resulted in significantly reduced periodontal bone resorption. This study suggests thatP. gingivalisinfection-associated periodontal bone resorption is RANKL dependent and is accompanied by increased local infiltration of RANKL-expressing T and B cells.

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