Cancer pain relief achieved by disrupting tumor-driven semaphorin 3A signaling in mice

Takehiko Maeda, Daisuke Yamada, Kohichi Kawahara

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Cancer-induced bone pain (CIBP) is the most common pain arising from cancer and is inadequately managed with current standard therapeutics. While the etiology of CIBP remains to be fully elucidated, increasing evidence suggests that CIBP is uniquely complex. We tested whether semaphorin 3A (Sema3A) signals were involved in the development of CIBP in mice. The mouse model employed for CIBP – mice inoculated with Lewis lung carcinoma (LLC) cells injected into the femur intramedullary space – showed progressive decline in the weight bearing of the ipsilateral hind limb. The LLC cell inoculation resulted in a progressive increase in Sema3A mRNA expression over time and an increase in the number of Sema3A-immunoreactive cells in the ipsilateral femur. To define the role of Sema3A in development of CIBP, we employed a lentiviral expression system to establish a stable LLC cell line expressing scrambled shRNA for the control group (LLC/scramble) and shRNAs directed against Sema3A mRNA for the loss-of-function group (LLC/shSema3A). Inoculation of LLC/shSema3A did not cause upregulation of Sema3A mRNA expression and proliferation of the inoculated cells in the femur compared to that in mice inoculated with LLC/scramble. Mice inoculated with LLC/shSema3A, but not LLC/scramble, showed an attenuation of the significant decline in the weight bearing of the ipsilateral hind paw. Our findings indicate that Sema3A serves as a potential therapeutic target for CIBP.

Original languageEnglish
Pages (from-to)147-151
Number of pages5
JournalNeuroscience Letters
Volume632
DOIs
Publication statusPublished - Oct 6 2016
Externally publishedYes

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Keywords

  • Cancer-induced bone pain
  • Semaphorin 3A
  • Tumor inoculation
  • Weight bearing asymmetry

ASJC Scopus subject areas

  • Neuroscience(all)

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