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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 3/2011

01-03-2011 | Translational Research and Biomarkers

In Vitro Sarcoma Cells Release a Lipophilic Substance That Activates the Pain Transduction System via TRPV1

Authors: Meeghan A. Lautner, MD, Shivani B. Ruparel, MS, PhD, Mayur J. Patil, MS, Kenneth M. Hargreaves, PhD

Published in: Annals of Surgical Oncology | Issue 3/2011

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Abstract

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 rhabdomyosarcoma CM 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 side-effects.
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Metadata
Title
In Vitro Sarcoma Cells Release a Lipophilic Substance That Activates the Pain Transduction System via TRPV1
Authors
Meeghan A. Lautner, MD
Shivani B. Ruparel, MS, PhD
Mayur J. Patil, MS
Kenneth M. Hargreaves, PhD
Publication date
01-03-2011
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 3/2011
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-010-1328-1

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