title: Impact of the Sensory Neurons on Melanoma Growth In Vivo.
abstract: Nerve endings are often identified within solid tumors, but their impact on the tumor growth and progression remains poorly understood. Emerging data suggests that the central nervous system may affect cancer development and spreading via the hypothalamic-pituitary-adrenal axis and autonomous nervous system. However, the role of the afferent sensory neurons in tumor growth is unclear, except some reports on perineural invasion in prostate and pancreatic cancer and cancer-related pain syndrome. Here, we provide the results of primary testing of the concept that the interaction between melanoma cells and sensory neurons may induce the formation of tumor-supporting microenvironment via attraction of immune regulatory cells by the tumor-activated dorsal root ganglion (DRG) neurons. We report that despite DRG cells not directly up-regulating proliferation of melanoma cells in vitro, presence of DRG neurons allows tumors to grow significantly faster in vivo. This effect has been associated with increased production of chemokines by tumor-activated DRG neurons and attraction of myeloid-derived suppressor cells both in vitro and in vivo. These initial proof-of-concept results justify further investigations of the sensory (afferent) nervous system in the context of tumorigenesis and the local protumorigenic immunoenvironment.
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania,United States of America.
authors.forename: Anton A
authors.identifier: 0000-0001-7378-983X
authors.initials: AA
authors.lastname: Keskinov
authors.affiliation: Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors.forename: Victor
authors.initials: V
authors.lastname: Tapias
authors.affiliation: Department of Cell Biology and Physiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Watkins
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania,United States of America.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania,United States of America.|Department of Immunology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania,United States of America.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Shurin
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania,United States of America.
authors.forename: Galina V
authors.initials: GV
authors.lastname: Shurin
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D005434:Flow Cytometry; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured