CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Prosaposin, tumor-secreted protein, promotes pancreatic cancer progression by decreasing tumor-infiltrating lymphocytes.
Prosaposin, tumor-secreted protein, promotes pancreatic cancer progression by decreasing tumor-infiltrating lymphocytes.
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肿瘤细胞产生的糖蛋白参与癌症进展、转移和免疫反应，并可作为潜在的治疗靶点。鉴于胰腺导管腺癌（PDAC）因其独特的肿瘤微环境（以抗肿瘤T细胞浸润低为特征）而导致的不良预后，我们假设肿瘤来源的糖蛋白可能参与调节肿瘤微环境。
我们采用串联质量标签标记的糖蛋白质组学方法研究了三株人PDAC细胞系的培养基，并试图鉴定PDAC细胞分泌的关键蛋白。在鉴定出的糖蛋白中，我们研究了prosaposin（PSAP）对PDAC进展的功能性贡献。PSAP在多种PDAC细胞系中高表达；然而，敲低内源性PSAP表达并未影响增殖和迁移能力。基于切除的人PDAC组织的免疫组织化学分析，PSAP高表达与PDAC患者的不良预后相关。
值得注意的是，PSAP高表达的肿瘤中CD8 + T细胞浸润显著低于PSAP低表达的肿瘤。此外，PSAP刺激降低了外周血单核细胞中CD8 + T细胞的比例。
最后，在原位移植模型中，PSAP shRNA组的CD8 + T细胞数量显著增加，导致肿瘤体积较对照shRNA组减小。PSAP抑制CD8 + T细胞浸润，从而促进PDAC进展。
然而，仍需进一步研究以确定本研究是否有助于开发针对PDAC的新型免疫调节疗法。
Glycoproteins produced by tumor cells are involved in cancer progression, metastasis, and the immune response, and serve as possible therapeutic targets. Considering the dismal outcomes of pancreatic ductal adenocarcinoma (PDAC) due to its unique tumor microenvironment, which is characterized by low antitumor T-cell infiltration, we hypothesized that tumor-derived glycoproteins may serve as regulating the tumor microenvironment.
We used glycoproteomics with tandem mass tag labeling to investigate the culture media of three human PDAC cell lines, and attempted to identify the key secreted proteins from PDAC cells. Among the identified glycoproteins, prosaposin (PSAP) was investigated for its functional contribution to PDAC progression.
PSAP is highly expressed in various PDAC cell lines; however, knockdown of intrinsic PSAP expression did not affect the proliferation and migration capacities. Based on the immunohistochemistry of resected human PDAC tissues, high PSAP expression was associated with poor prognosis in patients with PDAC.
Notably, tumors with high PSAP expression showed significantly lower CD8 + T-cell infiltration than those with low PSAP expression.
Furthermore, PSAP stimulation decreased the proportion of CD8 + T cells in peripheral blood monocytes.
Finally, in an orthotopic transplantation model, the number of CD8 + T cells in the PSAP shRNA groups was significantly increased, resulting in a decreased tumor volume compared with that in the control shRNA group. PSAP suppresses CD8 + T-cell infiltration, leading to the promotion of PDAC progression.
However, further studies are warranted to determine whether this study contributes to the development of a novel immunomodulating therapy for PDAC.
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →
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