Inhibition of pentraxin 3 in glioma cells impairs proliferation and invasion in vitro and in vivo

Abstract

Pentraxin 3 (PTX3) is an inflammatory molecule that is involved in immune responses, inflammation, and cancer. Recent evidence suggests that PTX3 plays a critical role in tumor progression; however, its impact on the biological function of gliomas remains unknown. In the present study, immunohistochemical staining showed that patients with high-grade gliomas exhibited increased expression levels of PTX3 compared to those with low-grade gliomas (P < 0.001). Furthermore, knockdown of PTX3 in GBM8401 cells inhibits proliferation, increases p21 protein levels, and decreases cyclin D1 protein levels, resulting in cell cycle arrest at the G0/G1 phase. In addition, knockdown of PTX3 significantly decreases GBM8401 cell migration and invasion through the downregulation of matrix metalloproteinase-1 and -2 (MMP-1 and MMP-2) expression. In a GBM8401 xenograft animal model, PTX3 knockdown decreases tumor growth in vivo. In conclusion, PTX3 plays an important role in glioma cell proliferation and invasion, and may thus serve as a novel potential therapeutic target in the treatment of gliomas.

Inflammatory biomarkers and cancer: CRP and suPAR as markers of incident cancer in patients with serious nonspecific symptoms and signs of cancer

“…To our knowledge, this is the first study investigating the association between MBL, ficolin‐1–3 and pentraxin‐3 with incident cancer in a group of NSSC patients. Several studies have previously found an association between increased levels of these biomarkers and various organ‐specific cancers . For example, pentraxin‐3 levels have been found to be associated with lung cancer, gliomas and prostate cancer, and high pentraxin‐3 expression was found to be associated with poor survival in lung cancer .…”

“…Several studies have previously found an association between increased levels of these biomarkers and various organ-specific cancers. 7,8,10,[12][13][14][15] For example, pentraxin-3 levels have been found to be associated with lung cancer, 7 gliomas 8,9 and prostate cancer, 10 and high pentraxin-3 expression was found to be associated with poor survival in lung cancer. 7,43 Similarly, ficolin-1 (M-ficolin) has been associated with colorectal cancer, 12 and serum concentrations of ficolin-2 (L-ficolin) and ficolin-3 (H-ficolin) have been found to be increased in patients with malignant ovarian tumors compared to benign tumors or normal ovaries.…”

“…[4][5][6] Fluid-phase pattern recognition receptors (PRRs) of the innate immune system, including pentraxin-3, mannose-binding lectin (MBL), ficolin-1, ficolin-2 and ficolin-3, recognize pathogens and modified self-molecules and have been found to be associated with cancer. [7][8][9][10][11][12][13][14][15][16][17] Another novel biomarker in this setting is the soluble urokinase plasminogen activator receptor (suPAR) which reflects inflammatory activity. suPAR is the soluble form of uPAR which, in cancer, is expressed on cancer cells and stromal cells.…”

Pentraxins in the activation and regulation of innate immunity

“…Beside the role as oncosuppressor, few reports outline a pro‐tumoral role of PTX3. In gastric cancer and head and neck tumors, PTX3 promotes tumor cell migration and invasion, while in human glioma, the protein sustains tumor cell proliferation . In addition, in gastric cancer, PTX3 silencing suppresses cancer‐related inflammation.…”

“…In gastric cancer and head and neck tumors, PTX3 promotes tumor cell migration and invasion, [136][137][138] while in human glioma, the protein sustains tumor cell proliferation. 139 In addition, in gastric cancer, PTX3 silencing suppresses cancer-related inflammation. These contrasting results suggest that further studies will be necessary to define the real significance of PTX3 in the regulation of tumor-associated inflammation.…”