In vitro sarcoma cells release a lipophilic substance that activates the pain transduction system via TRPV1

Meeghan A. Lautner, Shivani B. Ruparel, Mayur J. Patil, Kenneth M. Hargreaves

Research output: Contribution to journalArticle

6 Scopus citations


Background. Despite success in treating many forms of cancer, pain associated with malignancy remains a serious clinical issue with a poorly understood etiology. This study determined if certain sarcoma cell lines produced a soluble factor that activates the TRPV1 ion channel expressed on nociceptive sensory neurons, thereby activating a major pain transduction system. Materials and Methods. Trigeminal ganglia were harvested from rats and cultured. A rhabdomyosarcoma (CRL1598) and osteosarcoma (CRL 1543) cell line were grown to 75% confluency. Conditioned media (CM) was collected after 24 h of exposure and subjected to reverse phase chromatography. Neuronal activation in the presence of CM was measured using iCGRP RIA and calcium imaging after treatment with vehicle or I-RTX, a potent TRPV1 antagonist. Data were analyzed by ANOVA/Bonferroni or t test. Results. The rhabdomyosarcoma CM produced a 4-fold increase in iCGRP release compared with control media (P<0..001). The osteosarcoma cell line CM produced a 7-fold increase in iCGRP release compared with control media (P<0..001). This evoked iCGRP release was via TRPV1 activation since the effect was blocked by the antagonist I-RTX. The application of rhabdomyosarcomaCM produced about a 4-fold increase in [Ca2+]I levels (P<0..001), and this effect was blocked by pretreatment with the TRPV1 antagonist, I-RTX. Conclusions. We have shown that certain sarcoma cell lines produce a soluble, lipophilic factor that activates the peripheral nociceptor transduction system via TRPV1 activation, thereby contributing to cancer pain. Further investigations are needed to develop tumor-specific analgesics that do not produce unwanted or harmful sideeffects.

Original languageEnglish (US)
Pages (from-to)866-871
Number of pages6
JournalAnnals of Surgical Oncology
Issue number3
StatePublished - Mar 1 2011


ASJC Scopus subject areas

  • Surgery
  • Oncology

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