The HMGB1/RAGE axis induces bone pain associated with colonization of 4T1 mouse breast cancer in bone

Okui, Tatsuo; Hiasa, Masahiro; Ryumon, Shoji; Ono, Koji; Kunisada, Yuki; Ibaragi, Soichiro; Sasaki, Akira; Roodman, G. David; White, Fletcher A.; Yoneda, Toshiyuki

doi:10.1016/j.jbo.2020.100330

Cited by 26 publications

(21 citation statements)

References 38 publications

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“…The p73 protein is known to regulate the genes responsible for metastasis, but the direct association is not always established. For example, HMGB1, a putative p73 target that can regulate p73-mediated transactivation [ 129 , 130 ], is associated with EMT, metastasis, and poor prognosis in breast, lung, and other cancer types [ 55 , 131 , 132 , 133 ].…”

Section: Activation Of Invasion and Metastasismentioning

confidence: 99%

Dual Role of p73 in Cancer Microenvironment and DNA Damage Response

Rozenberg

Zvereva

Dalina

et al. 2021

Cells

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Understanding the mechanisms that regulate cancer progression is pivotal for the development of new therapies. Although p53 is mutated in half of human cancers, its family member p73 is not. At the same time, isoforms of p73 are often overexpressed in cancers and p73 can overtake many p53 functions to kill abnormal cells. According to the latest studies, while p73 represses epithelial–mesenchymal transition and metastasis, it can also promote tumour growth by modulating crosstalk between cancer and immune cells in the tumor microenvironment, M2 macrophage polarisation, Th2 T-cell differentiation, and angiogenesis. Thus, p73 likely plays a dual role as a tumor suppressor by regulating apoptosis in response to genotoxic stress or as an oncoprotein by promoting the immunosuppressive environment and immune cell differentiation.

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Section: Activation Of Invasion and Metastasismentioning

confidence: 99%

Dual Role of p73 in Cancer Microenvironment and DNA Damage Response

Rozenberg

Zvereva

Dalina

et al. 2021

Cells

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“…Pain is a common symptom in cancer patients ( Sheng and Zhang, 2020 ). Previous studies have shown that 85% of patients with lung, breast and prostate cancer appear bone metastasis, and about one-third of them was accompanied with bone cancer pain (BCP) symptoms ( Okui et al, 2021 ). Bone cancer pain (BCP) is a unique pain that includes features of nociceptive, neuropathic, and inflammatory pain ( de Clauser et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Metformin Attenuates Bone Cancer Pain by Reducing TRPV1 and ASIC3 Expression

Qian

Zhou

et al. 2021

Front. Pharmacol.

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Bone cancer pain (BCP) is a common pathologic pain associated with destruction of bone and pathological reconstruction of nervous system. Current treatment strategies in clinical is inadequate and have unacceptable side effects due to the unclear pathology mechanism. In the present study, we showed that transplantation of Walker 256 cells aggravated mechanical allodynia of BCP rats (**p < 0.01 vs. Sham), and the expression of ASIC3 (Acid-sensitive ion channel 3) and TRPV1 was obviously enhanced in L4-6 dorsal root ganglions (DRGs) of BCP rats (**p < 0.01 vs. Sham). ASIC3 and TRPV1 was mainly expressed in CGRP and IB4 positive neurons of L4-6 DRGs. While, TRPV1 but not ASIC3 was markedly upregulated in L4-6 spinal dorsal horn (SDH) of BCP rats (**p < 0.01 vs. Sham). Importantly, intrathecal injection of CPZ (a TRPV1 inhibitor) or Amiloride (an ASICs antagonist) markedly increased the paw withdraw threshold (PWT) of BCP rats response to Von Frey filaments (**p < 0.01 vs. BCP + NS). What’s more, intraperitoneally injection of Metformin or Vinorelbine markedly elevated the PWT of BCP rats, but reduced the expression of TRPV1 and ASIC3 in L4-6 DRGs and decreased the TRPV1 expression in SDH (*p < 0.05, **p < 0.01 vs. BCP + NS). Collectively, these results suggest an effective analgesic effect of Metformin on mechanical allodynia of BCP rats, which may be mediated by the downregulation of ASIC3 and TRPV1.

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“…Recent data showed that CABP is evoked in association with pathological neurogenesis, reprogramming and axonogenesis of SNs in concert with sensitization (a reduction in the threshold and an increase in the magnitude of a response to noxious stimulation) and excitation of SNs by a variety of neurotrophic factors, cytokines and chemokines that are produced in the tumor microenvironment in bone [8] , [10] , [33] . We and others found that cancer progression in bone promotes pathological sprouting and excitability of bone-innervating SNs, thereby eliciting CABP [34] , [35] , [36] , [37] . Thus, CABP is fundamentally a consequence of sensitization and excitation of SNs innervating bone.…”

Section: Pathophysiology Of Cabpmentioning

confidence: 76%

“…We have recently reported that CABP is induced following inoculation of 4T1 mouse breast cancer cells into the bone marrow cavity of tibiae of female BALB/c mice [37] . The 4T1 breast cancer cells aggressively grew with extensive osteolytic lesions in bone.…”

Section: Role Of Sns In Cancer Progression In Bone and Secondary Metastasis From Bonementioning

confidence: 99%

“…Further, as tumor grew in bone, these mice exhibited progressive CABP evaluated by the hind-paw mechanical hypersensitivity and increased expression of phosphorylated extracellular receptor kinase 1/2 (pERK1/2) and cyclic AMP-responsive element-binding protein (pCREB), two molecular markers of pain, in DRG SNs innervating bone. Using this model, we demonstrated that high mobility group box 1 (HMGB1) secreted by 4T1 breast cancer cells induces CABP via binding to the receptor for advanced glycation end products (RAGE) expressed on SNs [37] . Further, we found 4T1 breast cancer cells in tibiae create an acidic microenvironment, and promote sprouting and excitation of SNs in tibiae with increased expression and activation TRPV1 of SNs, thereby evoking CABP.…”

Section: Role Of Sns In Cancer Progression In Bone and Secondary Metastasis From Bonementioning

confidence: 99%

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