Jungwirth, Ute, van Weverwijk, Antoinette, Melake, Miriam J., Chambers, Ann F., Gao, Qiong, Fivaz, Marc ORCID: 0000-0003-1003-7934 and Isacke, Clare M. (2017) Generation and characterisation of two D2A1 mammary cancer sublines to model spontaneous and experimental metastasis in a syngeneic BALB/c host. Disease models & mechanisms. ISSN 1754-8403 (Print), 1754-8411 (Online) (doi:https://doi.org/10.1242/dmm.031740)

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Abstract

Studying the complex mechanisms underlying breast cancer metastasis and therapy response necessitates relevant in vivo models, particularly syngeneic models with an intact immune system. Two syngeneic spontaneously metastatic sublines, D2A1-m1 and D2A1-m2, were generated from the poorly metastasising BALB/c-derived D2A1 cell line by serial in vivo passaging. In vivo and in vitro analyses revealed distinct and shared characteristics of the metastatic D2A1-m1 and D2A1-m2 sublines. In particular, D2A1-m1 cells are more aggressive in experimental metastasis assays, while D2A1-m2 cells are more efficient at disseminating from the primary tumour in spontaneous metastasis assays. Surprisingly, classical metastasis-associated in vitro phenotypes such as enhanced proliferation, migration and invasion are reduced in the sublines compared to the parental cell line. Further, evasion of immune control cannot fully explain their enhanced metastatic properties. By contrast, both sublines show increased resistance to apoptosis when cultured in non-adherent conditions and, for the D2A1-m2 subline, increased 3D tumour spheroid growth. Moreover, the enhanced spontaneous metastatic phenotype of the D2A1-m2 subline is associated with an increased ability to recruit an activated tumour stroma. The metastatic D2A1-m1 and D2A1-m2 cell lines provide additional syngeneic models for investigating the different steps of the metastatic cascade and thereby represent valuable tools for breast cancer researchers. Finally, this study highlights that morphology and cell behaviour in 2D cell-based assays cannot be used as a reliable predictor of metastatic behaviour in vivo.

Item Type:	Article
Additional Information:	This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Uncontrolled Keywords:	mammary cancer, metastatic sublines, syngeneic, spontaneous metastasis, D2A1, BALB/c
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science Faculty of Education, Health & Human Sciences > School of Human Sciences (HUM)
Last Modified:	09 Oct 2021 04:45
URI:	http://gala.gre.ac.uk/id/eprint/18507

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