TABLE 2.

Schematic representation of the main stromal mediators involved in metastatic progression by estrogen and IIGF signaling.

Mediator	Regulator	Stromal cell of origin	Target cell/tissue	Metastasis-promoting function	References
Aromatase	Leptin, IL-6	CAFs, adipocytes, ASCs	BC cells and microenvironment	E2 production, cell proliferation, migration, angiogenesis	Luo et al., 2014; Kamat et al., 2015; Sabol et al., 2019
IGF-1 and IGF-2	Oncogenic mutations	CAFs, adipocytes, ASCs	BC cells and microenvironment	Homing, colonization, angiogenesis, EMT, stemness features, CAF activation	Lee et al., 2006, 2016; De Vincenzo et al., 2019
CTGF	E2, IIGFs	CAFs	CAFs, BC cells	Migration, invasion	Madeo and Maggiolini, 2010; De Marco et al., 2013, 2014
Notch	E2	CSCs	CSCs, BC cells	Stemness features, migration, EMT, homing	Pupo et al., 2014
Collagen/DDR1	IIGFs	CAFs	BC cells and microenvironment	Migration, ECM remodeling	Matà et al., 2016; Vella et al., 2017
HIF-1α/VEGF	E2, IGF-1	CAFs	ECs	Angiogenesis	De Francesco et al., 2014, 2017
IL-1β	E2	CAFs	BC cells and microenvironment	Migration, invasion	De Marco et al., 2016
FGF-2	E2	CAFs	BC cells and microenvironment		Santolla et al., 2019
OSM	Adipose stroma	Adipose stroma	CSCs	EMT, stemness features	Lapeire et al., 2014; Sanchez-Infantes et al., 2014; West et al., 2014
PDGF	IGF-1	CAFs	BC cells and microenvironment	EMT, ECM remodeling, intravasation	Pasanisi et al., 2008; Guo and Deng, 2018