Functional neuronal circuits promote disease progression in cancer.

Autor: Restaino AC; Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA.; University of South Dakota Sanford School of Medicine, Vermillion, SD, USA., Walz A; Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA., Vermeer SJ; Lincoln High School, Sioux Falls, SD, USA., Barr J; Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA., Kovács A; Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA., Fettig RR; Basic Biomedical Sciences Program, University of South Dakota, Vermillion, SD, USA., Vermeer DW; Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA., Reavis H; Penn Ovarian Cancer Research Center, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Williamson CS; Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA., Lucido CT; Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA., Eichwald T; Karolinska Institutet, Department of Pharmacology and Physiology, Solna, Sweden.; Queen's University, Department of Biomedical and Molecular Sciences, Kingston, Ontario, Canada., Omran DK; Penn Ovarian Cancer Research Center, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Jung E; Penn Ovarian Cancer Research Center, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Schwartz LE; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Bell M; Sanford Gynecologic Oncology, Sanford Health, Sioux Falls, SD, USA., Muirhead DM; Department of Pathology, Sanford Health, Sioux Falls, SD, USA., Hooper JE; Legacy Gift Rapid Autopsy Program, Johns Hopkins University, Baltimore, MD, USA., Spanos WC; Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA.; Sanford Ear, Nose and Throat Clinic, Sioux Falls, SD, USA., Drapkin R; Penn Ovarian Cancer Research Center, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Talbot S; Karolinska Institutet, Department of Pharmacology and Physiology, Solna, Sweden.; Queen's University, Department of Biomedical and Molecular Sciences, Kingston, Ontario, Canada., Vermeer PD; Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA.; University of South Dakota Sanford School of Medicine, Vermillion, SD, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2023 May 10; Vol. 9 (19), pp. eade4443. Date of Electronic Publication: 2023 May 10.
DOI: 10.1126/sciadv.ade4443
Abstrakt: The molecular and functional contributions of intratumoral nerves to disease remain largely unknown. We localized synaptic markers within tumors suggesting that these nerves form functional connections. Consistent with this, electrophysiological analysis shows that malignancies harbor significantly higher electrical activity than benign disease or normal tissues. We also demonstrate pharmacologic silencing of tumoral electrical activity. Tumors implanted in transgenic animals lacking nociceptor neurons show reduced electrical activity. These data suggest that intratumoral nerves remain functional at the tumor bed. Immunohistochemical staining demonstrates the presence of the neuropeptide, Substance P (SP), within the tumor space. We show that tumor cells express the SP receptor, NK1R, and that ligand/receptor engagement promotes cellular proliferation and migration. Our findings identify a mechanism whereby intratumoral nerves promote cancer progression.
Databáze: MEDLINE
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