The Basic Characteristics of the Pentraxin Family and Their Functions in Tumor Progression

Abstract

The pentraxin is a superfamily of proteins with the same domain known as the pentraxin domain at C-terminal. This family has two subgroups, namely; short pentraxins (C-reactive protein and serum amyloid P component) and long pentraxins (neuronal pentraxin 1, neuronal pentraxin 2, neuronal pentraxin receptor, pentraxin 3 and pentraxin 4). Each group shares a similar structure with the pentameric complexes arranged in a discoid shape. Previous studies revealed the functions of different pentraxin family members. Most of them are associated with human innate immunity. Inflammation has commonly been associated with tumor progression, implying that the pentraxin family might also participate in tumor progression. Therefore, we reviewed the basic characteristics and functions of the pentraxin family and their role in tumor progression.

Keywords: C-reactive protein; pentraxin 3; serum amyloid P component; the long pentraxins; tumor.

Figure 1

The role CRP on the innate immune system and tumor progression. The Fcγ receptor is expressed on the cell surface of immunocyte and multiple myeloma cells. CRP binds to Fcγ receptor to promote inflammation and tumor progression. The downstream pathways of this receptor in tumors include the PI3K/AKT/mTOR pathway, the ERK/NF-κB pathway and the p38/MAPK pathway. CRP regulates the expression of osteolytic cytokines in myeloma cells through p38 MAPK-Twist signaling.

Figure 2

Structure of the pentraxin family members. Protein structure of CRP (A) and SAP (B) from the PDB website and the hypothetical structure of the full monomer (C-terminal domain and N-terminal domain) of PTX3 (C), PTX4 (D), NPTX1 (E), NPTX2 (F), NPTXR (G) from the Swiss database.

Figure 3

Location of protein domain for each family member and their sequence homology. The outcome was predicted by the Pfam database. Pink box: Pentraxin domain. Green box: Coiled coil. Yellow box: Low complex region. Red box: Transmembrane region. A homology tree based on the similarity of the protein sequence of members of the pentraxin family is generated.

Figure 4

Survival analysis based on members of the pentraxin family from the Gepia website. Outcome of survival analysis predicted by the Gepia database including CRP (A), PTX4 (B,C) and the neuronal pentraxins (D–P).

Figure 5

Impact of PTX3 on overall survival and tumor phenotypes based on the Gepia dataset. (A) Breast invasive carcinoma. (B) Cervical squamous cell carcinoma and endocervical adenocarcinoma. (C) Head and Neck squamous cell carcinoma. (D) Kidney renal clear cell carcinoma. (E) Kidney renal papillary cell carcinoma. (F) Brain Lower Grade Glioma. (G) Lung adenocarcinoma. (H) Lung squamous cell carcinoma. (I) Mesothelioma. (J) Stomach adenocarcinoma. (K) Thyroid carcinoma. (L) Uterine Corpus Endometrial Carcinoma. The overall survival of tumor that cannot be predicted by PTX3 expression is not listed.

Figure 6

Mechanisms of pentraxin family in tumor progression. At the core is the pentraxin family and its seven members. The pentraxin family mainly participates in tumor metastasis, tumorigenesis, tumor cell apoptosis, tumor cell proliferation, and regulation of tumor microenvironment.