Expression of angiopoietin-like 4 fibrinogen-like domain (cANGPTL4) increases risk of brain metastases in women with breast cancer.

blood-brain barrier brain metastases breast cancer cANGPTL4 vascular permeability

Journal

Oncotarget
ISSN: 1949-2553
Titre abrégé: Oncotarget
Pays: United States
ID NLM: 101532965

Informations de publication

Date de publication:
05 May 2020
Historique:
received: 27 11 2019
accepted: 19 03 2020
entrez: 15 5 2020
pubmed: 15 5 2020
medline: 15 5 2020
Statut: epublish

Résumé

Brain metastases challenge daily clinical practice, and the mechanisms by which cancer cells cross the blood-brain barrier remain largely undeciphered. Angiopoietin-like 4 (ANGPTL4) proteolytic fragments have controversial biological effects on endothelium permeability. Here, we studied the link between ANGPTL4 and the risk of brain metastasis in cancer patients. From June 2015 to June 2016, serum samples from 113 cancer patients were prospectively collected, and ANGPTL4 concentrations were assessed. Using a murine model of brain metastases, we investigated the roles of nANGPTL4 and cANGPTL4, the two cleaved fragments of ANGPTL4, in the occurrence of brain metastases. An ANGPTL4 serum concentration over 0.1 ng/mL was associated with decreased overall-survival. Multivariate analyses found that only breast cancer brain metastases were significantly associated with elevated ANGPTL4 serum concentrations. 4T1 murine breast cancer cells were transfected with either In this study, we showed that a higher expression of Angiopoietin-like 4 Fibrinogen-Like Domain (cANGPTL4) was associated with an increased risk of brain metastases in women with breast cancer.

Sections du résumé

BACKGROUND BACKGROUND
Brain metastases challenge daily clinical practice, and the mechanisms by which cancer cells cross the blood-brain barrier remain largely undeciphered. Angiopoietin-like 4 (ANGPTL4) proteolytic fragments have controversial biological effects on endothelium permeability. Here, we studied the link between ANGPTL4 and the risk of brain metastasis in cancer patients.
MATERIALS AND METHODS METHODS
From June 2015 to June 2016, serum samples from 113 cancer patients were prospectively collected, and ANGPTL4 concentrations were assessed. Using a murine model of brain metastases, we investigated the roles of nANGPTL4 and cANGPTL4, the two cleaved fragments of ANGPTL4, in the occurrence of brain metastases.
RESULTS RESULTS
An ANGPTL4 serum concentration over 0.1 ng/mL was associated with decreased overall-survival. Multivariate analyses found that only breast cancer brain metastases were significantly associated with elevated ANGPTL4 serum concentrations. 4T1 murine breast cancer cells were transfected with either
CONCLUSIONS CONCLUSIONS
In this study, we showed that a higher expression of Angiopoietin-like 4 Fibrinogen-Like Domain (cANGPTL4) was associated with an increased risk of brain metastases in women with breast cancer.

Identifiants

pubmed: 32405335
doi: 10.18632/oncotarget.27553
pii: 27553
pmc: PMC7210011
doi:

Types de publication

Journal Article

Langues

eng

Pagination

1590-1602

Déclaration de conflit d'intérêts

CONFLICTS OF INTEREST Authors have no conflicts of interest to delcare.

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Auteurs

Tu Dao (T)

Université Paris Diderot, Inserm, UMR_S942, Paris, France.
Medical Oncology Department, National Cancer Hospital, Ha Noi, Vietnam.
Ha Noi Medical University, Oncology Department, Ha Noi, Vietnam.
Cancer Research and Clinical Trial Center, National Cancer Hospital, Ha Noi, Vietnam.
These authors contributed equally to this work.

Guillaume Gapihan (G)

Université Paris Diderot, Inserm, UMR_S942, Paris, France.
These authors contributed equally to this work.

Christophe Leboeuf (C)

Université Paris Diderot, Inserm, UMR_S942, Paris, France.

Diaddin Hamdan (D)

Université Paris Diderot, Inserm, UMR_S942, Paris, France.

Jean-Paul Feugeas (JP)

INSERM, U722-Paris, Paris, France.
Université de Franche Comté, Besançon, France.

Hanene Boudabous (H)

Oncology Department, Hôpital Avicenne, APHP, Bobigny, France.

Laurent Zelek (L)

Oncology Department, Hôpital Avicenne, APHP, Bobigny, France.
Université Paris 13, Villetaneuse, Paris, France.

Catherine Miquel (C)

Université Paris Diderot, Inserm, UMR_S942, Paris, France.
Pathology Department, Hôpital St Louis, APHP, Paris, France.

Thuan Tran (T)

Medical Oncology Department, National Cancer Hospital, Ha Noi, Vietnam.
Ha Noi Medical University, Oncology Department, Ha Noi, Vietnam.

Catherine Monnot (C)

Center for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, PSL Research University, Paris, France.

Stéphane Germain (S)

Center for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, PSL Research University, Paris, France.

Anne Janin (A)

Université Paris Diderot, Inserm, UMR_S942, Paris, France.
Pathology Department, Hôpital St Louis, APHP, Paris, France.
These authors are co-senior authors.

Guilhem Bousquet (G)

Université Paris Diderot, Inserm, UMR_S942, Paris, France.
Oncology Department, Hôpital Avicenne, APHP, Bobigny, France.
Université Paris 13, Villetaneuse, Paris, France.
These authors are co-senior authors.

Classifications MeSH