Table 3 Role of PAPP-A and IGFBP/IGF axis in BC

IGFBP-4 proteolysis

Leads to increase in IGF-I

Secreted along with IGF-I

Bovine mammary fibroblast cells

[98]

PAPP-A resistant IGFBP-4

Leads to sequestering of IGF-I

Retained tumor suppression; decreased angiogenesis and lung metastasis

4T1.2, orthotopic model of 4T1.2 BCs

[18, 99]

IGFBP-4 proteolysis

Due to increased PAPP-A levels from Skp2B overexpression

Putative p53 binding sites in PAPP-A gene

During pregnancy and lactation in the mice mammary glands

[81]

IGFBP-4

Co-expression with PAPP-A

Co-expression with IGFBP-4

HCC70, MDA-MB-468 and MDA-MB-231 cells

[16]

IGF-IR

Co-expression with PAPP-A

Co-expression with IGF-IR

HCC70, MDA-MB-468, HCC1954 and MDA-MB-231

[16]

IGF-IIR

Independent of PAPP-A expression

Expression with and without IGF-IIR

With PAPP-A: MDA-MB-468, HCC1954 and MDA-MB-231

Without PAPP-A: MCF-7, BT474, SKBR3, HCC1569, MDA-MB-453

[16]

IGFBP-5 proteolysis

Due to increased PAPP-A levels from increased collagen deposition

Higher in parous mice breast than in nulliparous mice

Transgenic mice overexpressing PAPP‐A in the mammary gland and MCF-7 BC cells

[102, 103]