Metastasis from the Tumor Interior and Necrotic Core Formation Are Regulated by Breast Cancer-derived Angiopoietin-like 7

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2023 Feb 28

PMID 36853945

Authors

Ami Yamamoto

Yin Huang

Brad A Krajina

Margaux McBirney

Andrea E Doak

Sixuan Qu

Carolyn L Wang

Michael C Haffner

Kevin J Cheung

Affiliations

Soon will be listed here.

Abstract

Necrosis in the tumor interior is a common feature of aggressive cancers that is associated with poor clinical prognosis and the development of metastasis. How the necrotic core promotes metastasis remains unclear. Here, we report that emergence of necrosis inside the tumor is correlated temporally with increased tumor dissemination in a rat breast cancer model and in human breast cancer patients. By performing spatially focused transcriptional profiling, we identified angiopoietin-like 7 (Angptl7) as a tumor-specific factor localized to the perinecrotic zone. Functional studies showed that Angptl7 loss normalizes central necrosis, perinecrotic dilated vessels, metastasis, and reduces circulating tumor cell counts to nearly zero. Mechanistically, Angptl7 promotes vascular permeability and supports vascular remodeling in the perinecrotic zone. Taken together, these findings show that breast tumors actively produce factors controlling central necrosis formation and metastatic dissemination from the tumor core.

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