Proteomics reveals the function reverse of MPSSS‐treated prostate cancer‐associated fibroblasts to suppress PC‐3 cell viability via the FoxO pathway

Abstract

Prostate cancer‐associated fibroblasts (prostate CAFs) are essential components of the tumor microenvironment and can promote tumor progression through their immunosuppressive functions. MPSSS, a novel polysaccharide purified from Lentinus edodes , has been reported to have anti‐tumor activity. MPSSS could also inhibit the immunosuppressive function of prostate CAFs, which has been demonstrated through that the secretome of MPSSS‐treated prostate CAFs could inhibit the proliferation of T cells. However, how the secretome of MPSSS‐treated prostate CAFs influence prostate cancer progression is still unclear. Interestingly, we found that the low molecular weight (3–100kD) secretome of prostate CAFs (lmwCAFS) could promote the growth of PC‐3 cells, while that of MPSSS‐treated prostate CAFs (MT‐lmwCAFS) could inhibit their growth. We carried out comparative secretomic analysis of lmwCAFS and MT‐lmwCAFS to identify functional molecules that inhibit the growth of PC‐3 cells, and proteomic analysis of lmwCAFS‐treated PC‐3 cells and MT‐lmwCAFS‐treated PC‐3 cells to investigate the underlying molecular mechanism. These analyses suggest that TGF‐β3 from MT‐lmwCAFS may inhibit the growth of PC‐3 cells. The validated experiments revealed that TGF‐β3 from MT‐lmwCAFS activated p21 expression in PC‐3 cells by regulating the FoxO pathway thereby inducing G0/G1 cell cycle arrest of PC‐3 cells. Overall, our data demonstrated that MPSSS reversed the ability of prostate CAFs to suppress the cell viability of PC‐3 cells, which might provide a potential therapeutic strategy to prevent prostate cancer progression.

Proteomic Research on the Antitumor Properties of Medicinal Mushrooms

“…Coimmunoprecipitation experiments in PC-3 cells showed that smad3-smad4 complex, which is a mediator of TGF-β pathway, was indeed activated by MT-lmwCAFS and interacted with the FoxO3 protein. In conclusion, TGF-β induces cell cycle arrest via FoxO pathway [96]. This study was in accordance with others that confirm that upregulated TGF-β expression is relevant in tumor cell cycle arrest [102].…”

“…Zhang et al investigated anti-tumor activity of MPSSS, a novel polysaccharide purified from Lentinus edodes on cancer-associated fibroblasts (CAFs), which are the essential component of the tumor immunosuppressive microenvironment [96]. A previous study from the same group showed that MPSSS inhibits tumor growth in vivo and can prevent the immunosuppressive function of prostate CAFs [97,98].…”

Identifying driver modules based on multi‐omics biological networks in prostate cancer

“…It can be seen from Table 5 that the eight members of the TP53 module participate in the FoxO signalling pathway. Regulation of the FoxO signalling pathway inhibits the functional reversal of the PC‐3 cell viability, thereby achieving the purpose of treating prostate cancer [ 45 ]. The p ‐value of the TP53 module is 1.13E‐03 in the Wnt signal pathway.…”

FoxO Transcription Factors: Applicability as a Novel Immune Cell Regulators and Therapeutic Targets in Oxidative Stress-Related Diseases

“…Glucosamine suppress lung cancer cell proliferation by affecting the transcriptional activity of FoxOs through inhibition of p27kip1 and p21cip1, which are involved in cell cycle arrest, and Bim and FasL, which are involved in apoptosis [ 120 ]. In addition, MPSSS, a novel polysaccharide purified from Lentinus edodes , has been reported to have anti-tumor activity [ 121 ]. M .…”