胰腺导管腺癌(PDAC)因沉默的发展和转移特点，以及低于10%的5年生存率而高度恶性。PDAC以大量的基质调节为特征，其通过细胞外基质/细胞相互作用影响癌症的发展。弹性蛋白是细胞外基质的关键元素。弹性蛋白降解产物(EDPs)通过调节细胞增殖、迁移和侵袭等许多生物过程发挥作用。本研究的目的是首次表征两个具有共识序列“GxxPG”和“GxPGxGxG”(VG-6和AG-9)对PDAC发展的影响。最近发现的核糖体蛋白SA(RPSA)在肿瘤细胞表面作为EDPs的新受体发挥作用，进而加剧了不良预后。将人类PDAC MIA PaCa-2/eGFP-FLuc+细胞通过编码绿色荧光蛋白(GFP)和萤火虫荧光素(FLuc)的自制慢病毒载体转导后，将6周龄的女性瑞士裸鼠Nu(Ico)-Foxn1nu皮下注射，并进行三次AG-9(n=4)、VG-6(n=5)或PBS(n=5)治疗。通过多模式成像(生物发光成像(BLI)、荧光成像(FLI)和磁共振成像(MRI))检测EDP对PDAC的影响。同时，使用卡尺测量肿瘤体积，并在体内研究结束时进行免疫组织化学检测。在体外通过光学成像验证MIA PaCa-2细胞后，我们证明EDP加剧了PDAC小鼠模型中的肿瘤生长。虽然VG-6在某种程度上刺激了肿瘤生长，但AG-9对肿瘤生长的影响更大。我们表明，在PDAC模型中 RPSA表达与EDPs的潜在效应相关。通过多模式成像，我们可以纵向体内跟踪肿瘤的发展。我们发现，除了AG-9组外，所有组都显示成熟的血管在肿瘤的近处结束，AG-9组则显示成熟的血管正在穿入肿瘤，表明肿瘤血管化水平增加。我们的研究结果表明，AG-9通过增加肿瘤血管化强烈促进PDAC进展。©2023年。作者(在Springer Nature Limited的专属许可下)。

Pancreatic ductal adenocarcinoma (PDAC) is highly malignant with a very poor prognosis due to its silent development and metastatic profile with a 5-year survival rate below 10%. PDAC is characterised by an abundant desmoplastic stroma modulation that influences cancer development by extracellular matrix/cell interactions. Elastin is a key element of the extracellular matrix. Elastin degradation products (EDPs) regulate numerous biological processes such as cell proliferation, migration and invasion. The aim of the present study was to characterise for the first time the effect of two EDPs with consensus sequences "GxxPG" and "GxPGxGxG" (VG-6 and AG-9) on PDAC development. The ribosomal protein SA (RPSA) has been discovered recently, acting as a new receptor of EDPs on the surface of tumour cells, contributing to poor prognosis.Six week-old female Swiss nude nu/nu (Nu(Ico)-Foxn1nu) mice were subcutaneously injected with human PDAC MIA PaCa-2/eGFP-FLuc+ cells, transduced with a purpose-made lentiviral vector, encoding green fluorescent protein (GFP) and Photinus pyralis (firefly) luciferase (FLuc). Animals were treated three times per week with AG-9 (n = 4), VG-6 (n = 5) or PBS (n = 5). The influence of EDP on PDAC was examined by multimodal imaging (bioluminescence imaging (BLI), fluorescence imaging (FLI) and magnetic resonance imaging (MRI). Tumour volumes were also measured using a caliper. Finally, immunohistology was performed at the end of the in vivo study.After in vitro validation of MIA PaCa-2 cells by optical imaging, we demonstrated that EDPs exacerbate tumour growth in the PDAC mouse model. While VG-6 stimulated tumour growth to some extent, AG-9 had greater impact on tumour growth. We showed that the expression of the RPSA correlates with a possible effect of EDPs in the PDAC model. Multimodal imaging allowed for longitudinal in vivo follow-up of tumour development. In all groups, we showed mature vessels ending in close vicinity of the tumour, except for the AG-9 group where mature vessels are penetrating the tumour reflecting an increase of vascularisation.Our results suggest that AG-9 strongly increases PDAC progression through an increase in tumour vascularisation.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.