Pleiotrophin in Mammary Gland Development and Breast Cancer: A Comprehensive Review of the Evidence

Pleiotrophin (PTN), a heparin-binding growth factor with potent mitogenic and angiogenic activity, has emerged as a key regulator of mammary gland biology and a potential driver of breast cancer progression. This review integrates current evidence on PTN's roles from normal mammary development, where it can delay ductal outgrowth, to triple negative breast cancer, where it promotes lung metastasis and correlates with poor survival. Though frequently reported as being overexpressed in breast cancer, the published data indicates that PTN transcription is reduced in cancer relative to normal breast cells. By contrast, serum PTN protein levels have been shown by multiple studies to be elevated in breast cancer patients relative to healthy controls. We examine the expression and function of PTN at a cellular level and explore the interplay between PTN and the tumour microenvironment. We evaluate preclinical models, clinical correlations, and emerging biomarker data that position PTN as a candidate prognostic indicator and therapeutic target. Despite growing interest, significant gaps remain regarding context-specific signalling. By integrating developmental and oncogenic perspectives, this review highlights PTN as a pivotal but underexplored factor in mammary gland physiology and breast cancer and outlines future research directions needed to translate PTN-targeted strategies into clinical benefit.