The Long Pentraxin 3: The Invisible Loom Weaving the Warp and Weft of Tumor Destiny

Tianyi Liu¹Manyu Li²Yuxi Cheng³Jialin Zou⁴Fengying Liu⁵Jie Dong⁵Cheng Qiu⁶Xuenan Peng⁷Deyang Kong⁷Zhifan Li⁷Xinyu Wang⁸Lanyu Li^5*

• ¹National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China, Beijing, China
• ²Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, China
• ³Lanzhou University First Hospital, Lanzhou, China
• ⁴Shandong University State Key Laboratory of Reproductive Medicine and Offspring Health, Jinan, China
• ⁵Central Hospital Affiliated to Shandong First Medical University, Jinan, China
• ⁶Peking Union Medical College Hospital Department of Orthopedics, Beijing, China
• ⁷Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
• ⁸Beijing Jishuitan Hospital Affiliated to Capital Medical University, Beijing, China

Pentraxins, which constitute a family of evolutionarily conserved pattern recognition molecules, are categorized into short and long branches. The long pentraxin 3 (PTX3) is a key member of the long pentraxin subfamily, while the C-reactive protein and serum amyloid P represent the short pentraxins. All pentraxins share a highly conserved C-terminal motif, an 8-amino acid sequence known as the pentraxin signature. PTX3 can be produced by a wide range of cell types, including immune cells such as dendritic cells, monocytes, and macrophages, as well as various non-immune cells, underscoring its pleiotropic roles in multiple pathophysiological processes. These include inflammation, infection, tissue repair, female fertility, and cancer. Although PTX3 engages commonly recognized signaling pathways, such as TNF-α, NF-κB, FGF, and PI3K/AKT, it can exert paradoxical effects in different cellular contexts, either promoting or inhibiting the proliferation, migration, invasion, and metastasis of cancer cells. This review provides a comprehensive overview of the multifaceted roles of PTX3 in various cancers, while also summarizing its functions in other physiological or pathological contexts. Furthermore, we critically examine the challenges and translational opportunities of PTX3, aiming to inform future research directions and therapeutic strategies for cancer management.