Table 1.

Pleiotropic effects of LIF: in vitro models

	Model	Effects of LIF	Ref
Reproduction/fertility	Healthy women volunteers and 8-week-old female mice.	LIF induces oocytes and graafian follicle expansion.	[176]
	In vitro studies from germ and testis cell culture.	LIF increases male germ cell maturation during spermatogenesis.	[177]
	Primary human endometrial epithelial cells and human endometrial epithelial cell line.	LIF and IL11 synergize to regulate cell adhesion of endometrial epithelial cells with blastocyst during implantation process.	[178]
Hormone regulation	NCI-H295R adrenocortical cells	LIF stimulates adrenal steroidogenesis.	[179]
Hematopoiesis	Bone marrow from 2 month old C3H/HeJ mice.	LIF and multi-CSF synergize to stimulate murine megakaryocyte production in vitro.	[180]
	Human mesenchymal stem cells, Treg cells.	LIF is involved in transplantation tolerance.	[15, 181]
Muscle	C2C12 myoblast cell line	LIF induces the proliferation of myoblasts.	[182]
	Model of JNK1−/− mice	There is a link between TNFalpha/LIF/JNK1 in myoblast proliferation/differentiation.	[183]
Vessels	IEM, murine endothelial cell line.	LIF, in synergy with FGF, regulates signals controlling capillary outgrowth.	[184]
Neurons	Neural crest cultures from CBA mouse embryos at stage E9.	LIF stimulates the generation of sensory neurons in culture of mouse neural crest.	[185]
	Human midbrain precursor cells.	LIF favours neurogenic differentiation of long-term propagated human midbrain precursor cells.	[186]
Eyes	Human retinal cells.	LIF allows CD133+ adult retinal cells to remain undifferentiated.	[187]
Ears	Corti1 cells.	LIF is involved in auditory cell proliferation.	[188]
Kidneys	Culture of rat metanephric mesenchyme.	LIF converts kidney mesenchyme to epithelia which then form nephrons.	[189]
Liver	Human hepatoma cell lines (HepG2).	LIF, with oncostatin M, induces hepcidin production in hepatoma cell lines. Hepcidin is considered to be the main factor responsible for the development of anemia in inflammatory conditions.	[190]
LIF in cancer	Cell lines derived from thyroid tumor specimen in human patients.		[191]
	Normal and tumoral mammary derived cell lines.	LIF inhibits (in non-tumorigenic cells) or induces (in tumorigenic cells) cell survival.	[192]
	ARMS and ERMS rhabdomyosarcoma cell lines.	LIF is involved in rhabdomyosarcoma-derived metastasis.	[193]
	In vivo and in vitro studies.	LIF is involved in melanoma tumor growth.	[194]
	In vivo and in vitro studies: BalbC/mice; SEKI cells; 8 human melanoma-derived cell lines.	LIF has a potential role in melanoma-induced bone metastasis.	[195]
	In vivo and in vitro studies: human glioma cell lines: U373MG and A172 and human primary cell cultures.	LIF and TGFbeta induce self renewal of glioma-initiating cells, promoting oncogenesis in vivo.	[196]