title: Schwann cells induce cancer cell dispersion and invasion.
abstract: Nerves enable cancer progression, as cancers have been shown to extend along nerves through the process of perineural invasion, which carries a poor prognosis. Furthermore, the innervation of some cancers promotes growth and metastases. It remains unclear, however, how nerves mechanistically contribute to cancer progression. Here, we demonstrated that Schwann cells promote cancer invasion through direct cancer cell contact. Histological evaluation of murine and human cancer specimens with perineural invasion uncovered a subpopulation of Schwann cells that associates with cancer cells. Coculture of cancer cells with dorsal root ganglion extracts revealed that Schwann cells direct cancer cells to migrate toward nerves and promote invasion in a contact-dependent manner. Upon contact, Schwann cells induced the formation of cancer cell protrusions in their direction and intercalated between the cancer cells, leading to cancer cell dispersion. The formation of these processes was dependent on Schwann cell expression of neural cell adhesion molecule 1 (NCAM1) and ultimately promoted perineural invasion. Moreover, NCAM1-deficient mice showed decreased neural invasion and less paralysis. Such Schwann cell behavior reflects normal Schwann cell programs that are typically activated in nerve repair but are instead exploited by cancer cells to promote perineural invasion and cancer progression.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Deborde
authors.forename: Tatiana
authors.initials: T
authors.lastname: Omelchenko
authors.forename: Anna
authors.initials: A
authors.lastname: Lyubchik
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Shizhi
authors.initials: S
authors.lastname: He
authors.forename: William F
authors.initials: WF
authors.lastname: McNamara
authors.forename: Natalya
authors.initials: N
authors.lastname: Chernichenko
authors.forename: Sei-Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Fernando
authors.initials: F
authors.lastname: Barajas
authors.forename: Chun-Hao
authors.initials: CH
authors.lastname: Chen
authors.forename: Richard L
authors.initials: RL
authors.lastname: Bakst
authors.forename: Efsevia
authors.initials: E
authors.lastname: Vakiani
authors.forename: Shuangba
authors.initials: S
authors.lastname: He
authors.forename: Alan
authors.initials: A
authors.lastname: Hall
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Wong
mesh_terms: D000818:Animals; D019002:CD56 Antigen / Q000378:metabolism*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D009361:Neoplasm Invasiveness; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D012583:Schwann Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D019002:CD56 Antigen; C522918:NCAM1 protein, human; C501063:Ncam1 protein, mouse