Walker 256 tumour cells increase substance P immunoreactivity locally and modify the properties of the blood-brain barrier during extravasation and brain invasion

Lewis, Kate M., Harford-Wright, Elizabeth, Vink, Robert, Nimmo, Alan J., and Ghabriel, Mounir N. (2013) Walker 256 tumour cells increase substance P immunoreactivity locally and modify the properties of the blood-brain barrier during extravasation and brain invasion. Clinical and Experimental Metastasis, 30 (1). pp. 1-12.

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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.

Item ID: 33292
Item Type: Article (Research - C1)
ISSN: 1573-7276
Keywords: brain metastases; blood–brain barrier; extravasation; substance P; neurogenic inflammation; endothelial barrier antigen
Funders: Neurosurgical Research Foundation
Date Deposited: 22 May 2014 04:26
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1112 Oncology and Carcinogenesis > 111201 Cancer Cell Biology @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1109 Neurosciences > 110903 Central Nervous System @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders @ 60%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920111 Nervous System and Disorders @ 40%
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