title: Walker 256 tumour cells increase substance P immunoreactivity locally and modify the properties of the blood-brain barrier during extravasation and brain invasion.
abstract: It is not yet known how tumour cells traverse the blood-brain barrier (BBB) to form brain metastases. Substance P (SP) release is a key component of neurogenic inflammation which has been recently shown to increase the permeability of the BBB following CNS insults, making it a possible candidate as a mediator of tumour cell extravasation into the brain. This study investigated the properties of the BBB in the early stages of tumour cell invasion into the brain, and the possible involvement of SP. Male Wistar rats were injected with Walker 256 breast carcinoma cells via the internal carotid artery and euthanised at 1, 3, 6 and 9 days post tumour inoculation. Culture medium-injected animals served as controls at 1 and 9 days. Evidence of tumour cell extravasation across the BBB was first observed at 3 days post-inoculation, which corresponded with significantly increased albumin (p < 0.05) and SP immunoreactivity (p < 0.01) and significantly reduced endothelial barrier antigen labelling of microvessels when compared to culture medium control animals (p < 0.001). By day 9 after tumour cell inoculation, 100 % of animals developed large intracranial neoplasms that had significantly increased albumin in the peri-tumoral area (p < 0.001). The increased SP immunoreactivity and altered BBB properties at 3 days post-inoculation that coincided with early tumour invasion may be indicative of a mechanism for tumour cell extravasation into the brain. Thus, extravasation of tumour cells into the brain to form cerebral metastases may be a SP-mediated process.
authors.affiliation: Discipline of Anatomy and Pathology, School of Medical Sciences, The University of Adelaide, Adelaide, South Australia, 5005, Australia.
authors.forename: Kate M
authors.initials: KM
authors.lastname: Lewis
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Harford-Wright
authors.forename: Robert
authors.initials: R
authors.lastname: Vink
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Nimmo
authors.forename: Mounir N
authors.initials: MN
authors.lastname: Ghabriel
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000098:blood supply / Q000473:pathology* / Q000556:secondary; D002199:Capillary Permeability; D002279:Carcinoma 256, Walker / Q000378:metabolism / Q000473:pathology*; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D013373:Substance P