Expression of angiopoietin-like 4 fibrinogen-like domain increases the risk of metastases

Volume 11, Number 18 of @Oncotarget reported that using a murine model of brain metastases, The Research Team investigated the roles of nANGPTL4 and cANGPTL4, the two cleaved fragments of ANGPTL4, in the occurrence of brain metastases.

Multivariate analyses found that only breast cancer brain metastases were significantly associated with elevated ANGPTL4 serum concentrations.

On tissue sections, compared to wild-type mice, mice injected with nANGPTL4 cells had significantly larger surface areas of lung metastases, and mice injected with cANGPTL4 had significantly larger surface areas of brain metastases.

Co-senior authors: Dr. Guilhem Bousquet from The Université Paris Diderot, Inserm, UMR_S942 in Paris, France, The Oncology Department, Hôpital Avicenne, APHP in Bobigny, France and The Université Paris 13, Villetaneuse in Paris, France as well as Dr. Anne Janin another member of The Université Paris Diderot, Inserm, UMR_S942 in Paris, France but also from The Pathology Department at The Hôpital St Louis, APHP in Paris, France said, "Breast cancer is a leading cause of cancer death in women."

"Breast cancer is a leading cause of cancer death in women."

- Dr. Guilhem Bousquet, The Université Paris Diderot, Inserm, UMR_S942, The Oncology Department, Hôpital Avicenne, APHP, and The Université Paris 13 & Dr. Anne Janin The Université Paris Diderot, Inserm, UMR_S942 and The Pathology Department at The Hôpital St Louis, APHP

Brain metastases occur in the progression of metastatic breast cancer in 15 to 40% cases, with a median survival of fewer than 15 months, challenging daily practice in oncology.

In a preclinical murine model of brain metastases using human breast cancer cell lines, ANGPTL4 mRNA and protein expression were associated with an increased risk of lung and brain metastases.

Figure 1: Elevated ANGPTL4 serum concentration is associated with shorter survival in the 38 women with breast cancer (A), and predicts the risk of brain metastases in these patients (B). ^*p < 0.05, ^**p < 0.01.

In the serum of 113 patients with different types of cancers, we initially assessed ANGPTL4 concentrations and showed that ANGPTL4 was elevated in women with breast cancer brain metastases.

Using an experimental murine model of breast cancer brain metastases, the authors investigated the role of each cleaved fragment of ANGPTL4 in the occurrence of brain metastases.

The Bousquet/Janin Research Team concluded in their Oncotarget Research Article, "our study 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. Our results open the way for further translational research on the role of the cANGPTAL4 fragment as a biomarker to predict the risk of breast cancer brain metastasis, and as a potential target for the prevention of these metastatic localizations."

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DOI - https://doi.org/10.18632/oncotarget.27553

Full text - https://www.oncotarget.com/article/27553/text/

Correspondence to - Guilhem Bousquet - guilhem.bousquet@aphp.fr and Anne Janin - anne.janin1165@gmail.com

Keywords - cANGPTL4, brain metastases, breast cancer, blood-brain barrier, vascular permeability

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