. Author manuscript; available in PMC: 2023 May 31.

Published in final edited form as: Cancer Metastasis Rev. 2023 Jan 5;42(1):255–276. doi: 10.1007/s10555-022-10076-w

Table 1.

In vivo models of dormancy and dormancy reawakening

Breast cancer models
					Lung		Bone	Brain
Cell line	Species	Host^a	Subtype^b	Injection route^c	Met.	Dormancy (weeks)	Met.	Dormancy (weeks)	Met.	Dormancy (weeks)	Findings	Ref.
T47D	Human	NSG, nude, NOD/SCID	ER⁺, PR⁺	IC, SQ, ortho	Yes	Yes (2)	Yes	Yes (8)	N.R.	N.R.	No growing metastases were detected 4–5 weeks after orthotopic injection, whereas ressection of the primary tumor induced growing bone metastases over the next 8 weeks (similar finding with MCF-7 cells). Genes most associated with actively growing bone metastases (vs. primary tumor) include MYC, CLDN1, IL1B, CRSK, and TNFRSF11A	[6-10]
T47D-DBM	Human	Nude	ER⁺, PR⁺	IC	N.R.	N.R.	Yes	Yes (6–8)	N.R.	N.R.	Dormancy in DBM cells is associated with the downregulation of mitosis genes whereas reawakening was associated with an increase ECM-encoding genes	[6]
MDA-MB-231-SCP6	Human	Nude	TN	IC	N.R.	N.R.	Yes	Yes (14)	N.R.	N.R.	SCP6, which lacks a signature of active bone metastatic growth (including CXCR4, IL11, CTGF, MMP1, OPN), remained dormant in bones 100 days after IC injection, with 10% of cases then showing progressing bone metastases (resulting in PD lines). Knockdown of VCAM-1, but not IL1B, TFPI2, MAGEB2 or KLRC1, decreased metastatic ability of PD1 cells	[11]
MCF-7	Human	Nude	ER⁺, PR⁺	IV, IC, ortho	Yes	Yes (9)	Yes	Yes (8)	N.R.	N.R.	See data for T47D and D2.0R cells	[8, 12-18]
HCC1954-LCC1	Human	Nude	TN	IC	N.R.	N.R.	N.R.	N.R.	Yes	Yes (12)	Latent LCC1 cells isolated from brains showed SOX9 upregulation and downregulation of MYC and WNT pathways	[19]
HMT-3522-T4-2	Human	NOD/SCID	TN	IC	Yes	Yes (8)	Yes	Yes (8)	Yes	Yes (8)	Notch1 factors secreted by endothelial cells increased the dormancy of HMT-3522-T4-2, whereas POSTN, TNC, VCAN, and FN1 added to co-cultures with endothelial and bone fibroblasts induced reawakening	[20]
ZR-75-1	Human	Nude	ER⁺, PR⁺	IC, ortho	N.R.	N.R.	Yes	Yes (8)	N.R.	N.R.	See data for T47D-DBM cells	[6]
4T07	Mouse	BALB/cfC3H	N.R.	IV	Yes	Yes (>12)	N.R.	N.R.	N.R.	N.R.	Transduction of retrovirus cDNA library from actively metastasizing 4T1 cells in 4T07 cells induced actively growing lung metastases showed that upregulation of Coco (encoded by Dand5) was sufficient to induce reawakening	[21]
D2-0R	Mouse	BALB/c	ER⁺	Ortho	Yes	Yes (2, 10)	Yes	N.R.	N.R.	N.R.	D2.0R dormancy in the lungs associated with local proliferation of AQP5⁺, PDPN⁺ alveolar type I cells (similar findings with 4T07 and MCF-7 cells). Dormant D2.0R cells isolated from lungs showed increases in the expression of known dormancy (BHLHE41, NR2F1), ECM (COL3A1, POSTN, TNC, LUM), and EMT genes (SNAI1, SNAI2, ZEB2, TWIST1) compared to isolated actively growing D2A1 cells	[14, 16, 22]
D2.A1-d	Mouse	BALB/c	TN	IV, IC	Yes	Yes (4)	Yes	Yes (1)	N.R.	N.R.	Compared to the parental D2A1 cells, which produced actively growing lung metastases, D2A1-d showed upregulation of EMT genes encoding Slug, Snail, Twist, and Zeb1. Injection of lipopolysaccharide induced active metastasis formation of D2A1-d cells in the lung and bone	[23]
EMT6	Mouse	BALB/c	ER⁺	Ortho	Yes	Yes (2)	N.R.	N.R.	N.R.	N.R.	EMT6 cells disseminate to lymph nodes and lung but fail to form macrometastases. Injection of EMT6-luc into EMT6-tumored BALB/c mice elicits a CD8-mediated anti-tumor immunity	[24]

NSG, NOD.Cg-Prkdc^scidIl2rg^tm1Wjl/SzJ; Nude; Foxn1^nu; NOD/SCID, NOD.Cg-Prkdc^scid/J

ER, estrogen receptor; PR, progesterone receptor; TN, triple negative

IC, intracardiac; SQ, subcutaneous; ortho, orthotopic mammary fat pad

DBM, dormant bone metastatic; ECM, extracellular matrix; IC, intracardiac; LCC, latency competent cancer; Met., metastasis; N.R., not reported; PD, post dormancy; SCP, single cell population