Table1_SFRP1 induces a stem cell phenotype in prostate cancer cells.DOCX

Prostate cancer (PCa) ranks second in incidence and sixth in deaths globally. The treatment of patients with castration-resistant prostate cancer (CRPC) continues to be a significant clinical problem. Emerging evidence suggests that prostate cancer progression toward castration resistance is associated with paracrine signals from the stroma. SFRP1 is one of the extracellular proteins that modulate the WNT pathway, and it has been identified as a mediator of stromal epithelium communication. The WNT pathway is involved in processes such as cell proliferation, differentiation, cell anchoring, apoptosis, and cell cycle regulation as well as the regulation of stem cell populations in the prostatic epithelium. In the present study, we explored the role of exogenous SFRP1 on the stem cell phenotype in prostate cancer. The results reveal that cancer stem cell markers are significantly increased by exogenous SFRP1 treatments, as well as the downstream target genes of the Wnt/-catenin pathway. The pluripotent transcription factors SOX2, NANOG, and OCT4 were also up-regulated. Furthermore, SFRP1 promoted prostate cancer stem cell (PCSC) properties in vitro, including tumorsphere formation, migration, bicalutamide resistance, and decreased apoptosis. Taken together, our results indicate that SFRP1 participates in the paracrine signaling of epithelial cells, influencing them and positively regulating the stem cell phenotype through deregulation of the WNT/β-catenin pathway, which could contribute to disease progression and therapeutic failure. This research increases our molecular understanding of how CRPC progresses, which could help us find new ways to diagnose and treat the disease.

前列腺癌（PCa）在全球范围内发病率位居第二，死亡率位居第六。对于去势抵抗性前列腺癌（CRPC）患者的治疗，仍然是一个重大的临床难题。新出现的证据表明，前列腺癌向去势抵抗性的进展与间质来源的旁分泌信号相关。SFRP1是调节WNT途径的细胞外蛋白之一，已被鉴定为间质上皮细胞通讯的介导者。WNT途径参与细胞增殖、分化、细胞锚定、细胞凋亡以及细胞周期调控等过程，并调节前列腺上皮中的干细胞群体。在本研究中，我们探讨了外源性SFRP1对前列腺癌细胞干性表型的作用。结果显示，外源性SFRP1处理显著增加了癌细胞干性标记物，以及Wnt/β-catenin途径的下游靶基因。多能转录因子SOX2、NANOG和OCT4的表达也上调。此外，SFRP1在体外促进了前列腺癌细胞干性（PCSC）的特性，包括肿瘤球形成、迁移、比卡鲁胺耐药性和细胞凋亡减少。综合来看，我们的研究结果指出，SFRP1参与了上皮细胞的旁分泌信号，通过WNT/β-catenin途径的失调影响并正调控干细胞表型，这可能导致疾病进展和治疗的失败。这项研究加深了我们对CRPC进展的分子理解，有助于我们寻找新的诊断和治疗疾病的方法。