Recent advances in understanding the molecular basis of infantile haemangioma development

Br J Dermatol. 2024 Oct 17;191(5):661-669. doi: 10.1093/bjd/ljae241.

Abstract

Infantile haemangioma (IH) - the most common vascular tumour of infancy - is comprised of diverse cell types, including endothelial cells, pericytes, fibroblasts and immune cells. IH is characterized by rapid proliferation followed by slow involution over 1-10 years. Most lesions regress spontaneously, but up to 10% can be disfiguring, with complications that require further medical treatment. Recent research has revealed the biological characteristics of IH, highlighting the involvement of angiogenesis and vasculogenesis during tumour formation. Gene expression profiling has provided vital insights into the underlying biological processes, with some of the key IH-related pathways identified, including vascular endothelial growth factor, the renin-angiotensin-aldosterone system, hypoxia-inducible factor 1α, Notch, platelet-derived growth factor, phosphoinositide 3-kinase/Akt/mammalian target of rapamycin, Janus kinase/signal transducers and activators of transcription, fibroblast growth factor, peroxisome proliferator-activated receptor-γ and insulin-like growth factor. Further evidence suggests extracellular matrix factors and hormone receptors regulate IH progression. In this review, we explore the molecular mechanisms involved in the proliferating, plateau and involuting phases of IH, identifying differentially expressed genes, targeted proteins and key signalling pathways. This knowledge will increase the broader understanding of vascular development, tissue remodelling and angiogenesis.

Plain language summary

Infantile haemangioma is a common vascular tumour (or birthmark) that affects babies. Less is known about the pathways involved in their development and progression. We look at the key proteins involved in the development of these tumours. These proteins help new blood vessels grow (called ‘angiogenesis’) when a tumour is just starting to appear. The area around the tumour becomes inflamed, and the immune system releases molecules called ‘cytokines’ that help new blood vessels grow and to increase the number of cells (called ‘proliferation’). Within a year, the tumours shrink and are gradually replaced by fatty tissue (called ‘spontaneous involution’). This phase is influenced by other proteins called ‘IGF’ and ‘PPAR-γ’, which encourage cell death and tissue remodelling. Hormone receptors and the area outside cells called the ‘extracellular matrix’ could be the key to understanding this change. Even though many protein signalling pathways are involved in the two phases, we still do not know exactly how the switch between them happens. This review explains the molecular mechanisms behind infantile haemangiomas, focusing on how the protein signalling pathways work together. Our research offers valuable insights for both researchers and clinicians in this field.

Publication types

  • Review

MeSH terms

  • Hemangioma* / genetics
  • Hemangioma* / pathology
  • Humans
  • Infant
  • Neovascularization, Pathologic*
  • Signal Transduction
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology