caa a22 4500 445335068 CHVBK 20180317142752.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1245/s10434-010-1328-1 doi (NATIONALLICENCE)springer-10.1245/s10434-010-1328-1 In Vitro Sarcoma Cells Release a Lipophilic Substance That Activates the Pain Transduction System via TRPV1 [Elektronische Daten] [Meeghan Lautner, Shivani Ruparel, Mayur Patil, Kenneth Hargreaves] 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 24h 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. Society of Surgical Oncology, 2010 Lautner Meeghan Department of Surgery, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA aut Ruparel Shivani Department of Endodonitcs, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA aut Patil Mayur Department of Endodonitcs, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA aut Hargreaves Kenneth Department of Surgery, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA aut Annals of Surgical Oncology Springer-Verlag 18/3(2011-03-01), 866-871 1068-9265 18:3<866 2011 18 10434 https://doi.org/10.1245/s10434-010-1328-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1245/s10434-010-1328-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lautner Meeghan Department of Surgery, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA aut NATIONALLICENCE 700 1- Ruparel Shivani Department of Endodonitcs, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA aut NATIONALLICENCE 700 1- Patil Mayur Department of Endodonitcs, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA aut NATIONALLICENCE 700 1- Hargreaves Kenneth Department of Surgery, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA aut NATIONALLICENCE 773 0- Annals of Surgical Oncology Springer-Verlag 18/3(2011-03-01), 866-871 1068-9265 18:3<866 2011 18 10434 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer