Department of General Thoracic Surgery, Saitama Medical Centre, Saitama Medical University, Saitama, Japan.
Department of General Thoracic Surgery, Saitama Medical Centre, Saitama Medical University, Saitama, Japan;
In Vivo. 2024 Nov-Dec;38(6):2752-2760. doi: 10.21873/invivo.13754.
BACKGROUND/AIM: The dynamic interplay between cancer cells and the microenvironment involves a wide range of intricate relationships that evolve during different stages of tumor progression. Recent attention has focused on high endothelial venules (HEVs), specialized endothelial cells in tumors with a unique cuboidal shape similar to those in lymph nodes. Previous animal studies have shown that normalization of tumor angiogenesis through anti-VEGFR2 therapy promotes HEV formation. However, few reports exist regarding the relationship between HEVs and preexisting blood vessels or interstitial fibers. In this study, we histologically examined whether tumor vascular structure correlates with HEV neogenesis.
A total of 109 patients with pathological stage I lung adenocarcinoma who had undergone curative lung resection at our Institute between 2012 and 2016 were included. HEVs were identified by anti-peripheral node addressin (PNAd) staining. Immunostaining and Elastica-Masson-Goldner staining were performed on tumor sections and quantified.
PNAd-positive cells were identified in 102 (93.6%) patients. Nearly all PNAd-positive cells were located within or near immune cell clusters. We investigated the correlation between microvessel structures or interstitial fibers and the number/density of PNAd-positive vessels, but no significant correlation was found. Since PNAd-positive cells were concentrated in immune cell aggregates, we focused our analysis specifically on these regions. Immune cell aggregates with abundant PNAd-positive vessels had a greater microvessel density along with by rich collagen fiber production, and displayed a more mature morphological phenotype of HEVs.
The generation of PNAd-positive cells in tumors is governed by an angiogenetic mechanism distinct from that of broader tumor microenvironment. Furthermore, the accumulation of immune cells is associated with increased HEV maturation.
背景/目的：癌细胞与微环境之间的动态相互作用涉及到广泛的复杂关系，这些关系在肿瘤进展的不同阶段不断演变。最近的研究重点是高内皮小静脉（HEV），它是肿瘤中具有独特立方形状的特化内皮细胞，类似于淋巴结中的内皮细胞。之前的动物研究表明，通过抗 VEGFR2 治疗使肿瘤血管正常化可促进 HEV 的形成。然而，关于 HEV 与现有血管或间质纤维之间的关系的报道很少。在这项研究中，我们通过组织学检查来研究肿瘤血管结构是否与 HEV 的新生有关。
共纳入了 109 例在 2012 年至 2016 年期间在我院接受根治性肺切除术的病理 I 期肺腺癌患者。通过抗外周节点地址素（PNAd）染色鉴定 HEV。对肿瘤切片进行免疫染色和弹性纤维-马松-戈尔德纳染色，并进行定量分析。
在 102 例（93.6%）患者中鉴定出 PNAd 阳性细胞。几乎所有 PNAd 阳性细胞都位于免疫细胞簇内或附近。我们研究了微血管结构或间质纤维与 PNAd 阳性血管的数量/密度之间的相关性，但未发现显著相关性。由于 PNAd 阳性细胞集中在免疫细胞聚集物中，我们专门对这些区域进行了分析。富含 PNAd 阳性血管的免疫细胞聚集物具有更高的微血管密度和丰富的胶原纤维生成，并显示出更成熟的 HEV 形态表型。
肿瘤中 PNAd 阳性细胞的产生受一种不同于更广泛的肿瘤微环境的血管生成机制的控制。此外，免疫细胞的聚集与 HEV 成熟度的增加有关。
