Table 2.

Differential IGF1 isoforms (mRNA, protein) expression in human cancer cell lines and mechanisms of action noted in in vitro conditions.

		IGF1 mRNA Isoforms			IGF1 Propetides/Peptides
Human Cancer	Human Cell Lines	IGF1Ea (Class I/II)	IGF1Eb (Class I/II)	IGF1Ec (Class I/II)	Pro-Ea/Ea	Pro-Eb/Eb	Pro-Ec/Ec (MGF)	No of ref.
Breast cancer	MSF7	(+)↑ vs. Ec; class nt	(-)	(+); class nt	nt		(+) Ec peptide	[106]
		nt			nt		shEc - ↑cell proliferation and migration via ERK1/2	[170]
		nt			nt	rEb peptide - anticancer activity	nt	[168,169]
		nt			all pro-forms - ↑cell proliferation via the IGF1R; less capable of phosphorylating the IGF1R vs. mature IGF1			[16]
	MDA-MB-231	(+); class nt	(-)	(+)↑ vs. Ea; class nt	nt		(+) Ec peptide	[106]
		nt			nt		shEc did not ↑cell proliferation	[170]
		nt			nt	rEb peptide - anticancer activity	nt	[168,169,171,172]
	T47D	nt			all pro-forms - ↑cell proliferation via the IGF1R signaling, less capable of phosphorylating the IGF1R vs. mature IGF1			[16]
	ZR751	nt
Colorectal cancer	DLD1	(+) ≈ vs. Eb, ↑ vs. Ec; from class I/II	(+)↑ vs. Ec; from class I/II	(+) from class I/II	nt		(+) Ec peptide	[106]
	SW620	nt			nt		(+) Ec (MGF) peptide	[34]
	HT29	nt			nt		(+) Ec (MGF) peptide	[34]
		nt			nt	rEb peptide - anticancer activity	nt	[169]
Endometrial cancer	KLE	(+) all mRNA isoforms in stromal cells of eutopic and ectopic endometrium; (+) IGF1Ec - in glandular cells of ectopic endometrium			nt		sEc peptide (MGF) - ↑cell growth via an IGF1R-, INSR-independent mechanism	[107]
		(+)↑ vs. Eb; from class I/II	(+); from class I/II	(+)↑ vs. Ea&Eb; from class I/II	(+) pro-Ea; ↑ vs. other cells	nt	(+) Ec peptide; ↑ vs. other cells	[106]
Epithelial Cervical cancer	HeLa (HPV18+)	nt			nt	shEb peptide - ↑cell growth; in N	nt	[90]
		(+)↑ vs. Eb&Ec; in C	(+)↑ vs. Ec	(+)	(+) pro-IGF1A; ↑ vs. other cells	(+) pro-IGF1B in N; (+) hEb peptide in N	(+) Ec - very low expression	[31]
		(+) ≈ vs. Eb; from class II	(+) from class I	(+)↑ vs. Ea&Eb; from class I	nt		(+) Ec peptide; ↑ vs. other cells	[106]
Hepatocellular cancer	HepG2	(++)↑ vs. Ec	(+++)↑ vs. Ea and Ec	(+)	(+) pro-IGF1A; (-) Ea peptide	(-) pro-IGF1B;(+) hEb peptide in N	(+) Ec - very low expression	[31]
		nt			nt	rEb - anticancer activity	nt	[169]
	HuH7	(+) ≈ vs. Eb; from class I/II	(+) from class I	(+)↑ vs. Ea&Eb; from class I	nt		(+) Ec peptide	[106]
Lung cancer	NCI-H345	nt			nt	sEb peptide - ↑cell proliferation via an IGF1R-independent mechanism	nt	[84]
	A549	(+)↑ vs. Eb; from class I/II	(+) from class I	(+)↑ vs. Ea&Eb; from class I/II	nt		(+) Ec peptide	[106]
Melanoma malignum	SK-MEL28	(+)↑ vs. Eb&Ec; from class I/II	(+)↑ vs. Ec; ↑ vs. other cells; from class I	(+); from class I	nt	(+) pro-IGF1Eb; ↑ vs. other cells	(+) Ec peptide; ↑ vs. other cells	[106]
Osteosarcoma	U2OS	(+)↑ vs. Ec	(+)↑ vs. Ea and Ec	(+)	(+) pro-IGF1A; (-) Ea peptide	(-) pro-IGF1B;(+) hEb in N	(+) Ec - very low expression	[31]
		nt			nt	sEb peptide - ↑cell growth; in N	nt	[90]
	MG63	(+) from class I	(+)↑ vs. Ea; from class II	(+)↑ vs. Ea&Eb; from class I	nt		(+) Ec peptide; ↑ vs. other cells	[106]
		nt		(+) Ec - ↑ vs. MHos cells	nt		sEc peptide (MGF) - ↑cell proliferation and migration	[15]
		(+)	(-); (+) after exposure to DHT for 72 h	(+)	nt		sEc peptide - ↑cell growth via IGF1R/INSR/hybrid receptor-independent way	[14]
Prostate cancer	LnCaP	(+);↑ vs. Eb; ↑ vs. other cells; from class I/II	(+)↑ vs. other cells; from class I	(+)↑ vs. Ea&Eb; from class I	nt		(+) Ec peptide; ↑ vs. other cells	[106]
		nt		(+)	nt		(+) Ec peptide; sEc peptide - ↑cell growth via ERK1/2 and IGF1R/INSR/hybrid receptor-independent mechanism	[108]
	PC3	nt		(+)	nt		(+) Ec peptide; sEc - ↑cell growth via ERK1/2 and IGF1R/INSR/hybrid receptor-independent mechanism	[108]
		nt		(+)	nt		(+) Ec peptide; endogenous Ec peptide - ↑cell proliferation via ERK1/2	[166]
Myelogenous leukemia	K562	(+++)↑ vs. Eb&Ec	(++)↑ vs. Ec	(+)	(+) pro-IGF1A; (-) Ea peptide	(-) pro-IGF1B; ↑ Eb peptide vs. other cells; (+) hEb in N	(+) Ec - very low expression	[31]

Legend: (+)—positive expression; (++)—high expression; (+++)—overexpression; (-) lack of expression; ≈—comparable; ↑—higher or increased; &—and; C—cytoplasmic fraction/localization; DHT—dihydrotestosterone; h—hours; HPV—Human Papillomavirus; N—nucleus/nucleolus; nt—non tested; rEb—recombinant IGF1Eb isoform; shEb—synthetic human Eb peptide; sMGF—synthetic mechano-growth factor