Collective invasion in ductal and lobular breast cancer associates with distant metastasis

Clinical & Experimental Metastasis
Antoine A KhalilPeter Friedl

Abstract

Breast cancer undergoes collective tissue invasion and, in experimental models, can collectively metastasize. The prevalence of collective invasion and its contribution to distant metastasis in clinical disease, however, remains poorly defined. We here scored the adipose tissue invasion of primary invasive ductal carcinoma (IDC), expressing E-cadherin, and E-cadherin negative invasive lobular carcinoma (ILC) and identified predominantly collective invasion patterns (86/86 samples) in both carcinoma types. Whereas collective invasion in IDC lesions retained adherens junctions, multicellular clusters and "Indian files" in ILC, despite the absence of adherens junctions (AJ) proteins E-cadherin and β-catenin, retained CD44 at cell-cell contacts. By histomorphological scoring and semi-automated image analysis, we show that the extent of collective invasion into the adipose tissue correlated with decreased distant metastasis-free survival (5-year follow-up; hazard ratio: 2.32 and 2.29, respectively). Thus, collective invasion represents the predominant invasion mode in breast cancer, develops distinct junctional subtypes in IDC and ILC, and associates with distant metastasis, suggesting a critical role in systemic dissemination.

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Citations

Jul 13, 2018·Disease Models & Mechanisms·Olga IlinaPeter Friedl
Dec 19, 2018·International Journal of Molecular Sciences·Sunny Trivedi, Michelle Starz-Gaiano
Feb 2, 2019·PloS One·Shijie HeJeffrey J Fredberg
Apr 12, 2019·Clinical & Experimental Metastasis·Johannes A Eble, Stephan Niland
Aug 11, 2020·The Journal of Cell Biology·Antoine A KhalilPeter Friedl
Aug 25, 2020·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Andrew T PlygawkoKyra Campbell
Apr 25, 2018·American Journal of Respiratory Cell and Molecular Biology·Jennifer R Devlin, Emmy W Verschuren
Aug 30, 2018·Molecular Biology of the Cell·Ketki SawantJocelyn A McDonald
Aug 30, 2018·Journal of Cell Science·Kirsten GarnerSarah Woolner
Nov 27, 2019·Nature Ecology & Evolution· KshitizGünter P Wagner
Feb 28, 2020·Cell Death & Disease·Josephine VolovetzJustin D Lathia
May 21, 2020·Molecular Biology of the Cell·Emily F FoxTina L Tootle
Jul 3, 2019·Journal of Clinical Medicine·Sagar S Varankar, Sharmila A Bapat
May 15, 2019·Journal of Clinical Medicine·Gray W Pearson
Aug 23, 2019·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Andrea DisanzaGiorgio Scita
Oct 23, 2019·Seminars in Cancer Biology·Patricia Rousselle, Jean Yves Scoazec
Nov 5, 2020·Annals of Biomedical Engineering·Martha B Alvarez-ElizondoDaphne Weihs
Jun 9, 2021·Biochemical Society Transactions·Nishanth Belugali NatarajYosef Yarden

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Methods Mentioned

BETA
confocal microscopy

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