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Sympathetic activity in breast cancer and metastasis:partners in crime

Bone Research 2021年第1期9卷 26-36页

作者： Francisco Conceição Daniela M.Sousa Joana Paredes meriem lamghari I 3S-Instituto de Investigação e Inovação em Saúde Universidade do Porto4200-135 PortoPortugal INEB-Instituto Nacional de Engenharia Biomédica Universidade do Porto4200-135 PortoPortugal ICBAS-Instituto de Ciências Biomédicas Abel Salazar Universidade do Porto4050-313 PortoPortugal IPATIMUP-Instituto de Patologia e Imunologia Molecular da Universidade do Porto 4200-135 PortoPortugal FMUP-Faculdade de Medicina da Universidade do Porto 4200-319 PortoPortugal

The vast majority of patients with advanced breast cancer present skeletal complications that severely compromise their quality of *** cancer cells are characterized by a strong tropism to the bone *** engraftment and colonization of bone,breast cancer cells interact with native bone cells to hinder the normal bone remodeling process and establish an osteolytic“metastatic vicious cycle”.The sympathetic nervous system has emerged in recent years as an important modulator of breast cancer progression and metastasis,potentiating and accelerating the onset of the vicious cycle and leading to extensive bone ***,sympathetic neurotransmitters and their cognate receptors have been shown to promote several hallmarks of breast cancer,such as proliferation,angiogenesis,immune escape,and invasion of the extracellular *** this review,we assembled the current knowledge concerning the complex interactions that take place in the tumor microenvironment,with a special emphasis on sympathetic modulation of breast cancer cells and stromal ***,the differential action of epinephrine and norepinephrine,through eitherα-orβ-adrenergic receptors,on breast cancer progression prompts careful consideration when designing new therapeutic *** addition,the contribution of sympathetic innervation to the formation of bone metastatic foci is *** particular,we address the remarkable ability of adrenergic signaling to condition the native bone remodeling process and modulate the bone vasculature,driving breast cancer cell engraftment in the bone ***,clinical perspectives and developments on the use ofβ-adrenergic receptor inhibitors for breast cancer management and treatment are discussed.

关键词： breast metastasis invasion

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Osteoblasts are inherently programmed to repel sensory innervation

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Bone Research 2020年第3期8卷 343-355页

作者： Luis Leitao Estrela Neto Francisco Conceicao Ana Monteiro Marina Couto Cecilia JAlves Daniela MSousa meriem lamghari Instituto de Investigacao e Inovacao em Saude(i3S) Universidade do Porto4200-135 PortoPortugal Instituto de Engenharia Biomedica(INEB) Universidade do Porto4200-135 PortoPortugal Instituto de Ciencias Biomedicas Abel Salazar(ICBAS) Universidade do Porto4050-313 PortoPortugal

Tissue innervation is a complex process controlled by the expression profile of signaling molecules secreted by tissue-resident cells that dictate the growth and guidance of *** innervation is part of the neuronal network of the bone tissue with a defined spatiotemporal occurrence during bone ***,the current understanding of the mechanisms regulating the map of sensory innervation in the bone tissue is still ***,we demonstrated that differentiation of human mesenchymal stem cells to osteoblasts leads to a marked impairment of their ability to promote axonal growth,evidenced under sensory neurons and osteoblastic-lineage cells *** mechanisms by which osteoblast lineage cells provide this nonpermissive environment for axons include paracrine-induced repulsion and loss of neurotrophic factors *** identified a drastic reduction of NGF and BDNF production and stimulation of Sema3A,Wnt4;and Shh expression culminating at late stage of OB *** noted a correlation between Shh expression profile,OB differentiation stages,and OB-mediated axonal *** of Shh activity and signaling reversed the repulsive action of osteoblasts on sensory ***,to strengthen our model,we localized the expression of Shh by osteoblasts in bone ***,our findings provide evidence that the signaling profile associated with osteoblast phenotype differentiating program can regulate the patterning of sensory innervation,and highlight osteoblast-derived Shh as an essential player in this cue-induced regulation.

关键词： stimulation innervation reversed

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维普期刊数据库

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