Secreted Phosphoprotein 1 Represents a Therapeutic Target that Promotes the Progression of Ovarian Cancer by Driving...

The substantial infiltration of M2 macrophages in ovarian cancer (OC) signifies a poor prognosis, although the precise mechanisms remain unclear. The pivotal role played by Secreted phosphoprotein 1 (SPP1)-regulated macrophage polarization is evident. This study seeks to validate the role of SPP1 and macrophages within the OC tumor microenvironment (TME), potentially laying the groundwork for therapeutic approaches in ovarian cancer.

Using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we analyzed the immune infiltration characteristics in OC and unearthed the functions of macrophages. Additionally, we conducted immunohistochemistry (IHC) analysis to assess the expression of SPP1 and CD206 in OC tissues patients. Furthermore, we utilized flow cytometry to analyze the infiltration and polarization of CD206-positive cells. Subsequently, we employed ELISA to investigate SPP1 secretion and Western blot analysis to assess ARG1 protein expression. Next, transwell assays were utilized to evaluate the invasive capabilities of macrophages following SPP1 intervention. Finally, EDU assays were performed to analyze the proliferative capacity of OC cells.

We discovered that the infiltration of SPP1+ macrophages was a distinctive feature of OC TME. Our findings confirmed the high expression of CD206 in OC, along with abundant SPP1 expression in tissues exhibiting high CD206 levels. Furthermore, this association correlated closely with worse tumor staging, ascites, HRD mutations, and peritoneal metastasis, suggesting a poor prognosis associated with SPP1+CD206 infiltration. Additionally, we observed that lactate regulates the secretion of SPP1. Moreover, SPP1-high macrophages could promote the proliferation of ovarian cancer cells.

Our study identified the role of SPP1+macrophage in OC which may accelerated the metastasis and proliferation of OC.