Sanegre Sabina, Eritja Núria, de Andrea Carlos, Diaz-Martin Juan, Diaz-Lagares Ángel, Jácome María Amalia, Salguero-Aranda Carmen, García Ros David, Davidson Ben, Lopez Rafel, Melero Ignacio, Navarro Samuel, Ramon Y Cajal Santiago, de Alava Enrique, Matias-Guiu Xavier, Noguera Rosa
Cancer CIBER (CIBERONC), Madrid, Spain.
Department of Pathology, School of Medical, University of Valencia-INCLIVA, Valencia, Spain.
Front Cell Dev Biol. 2021 Jun 3;9:670185. doi: 10.3389/fcell.2021.670185. eCollection 2021.
The invasive tumor front (the tumor-host interface) is vitally important in malignant cell progression and metastasis. Tumor cell interactions with resident and infiltrating host cells and with the surrounding extracellular matrix and secreted factors ultimately determine the fate of the tumor. Herein we focus on the invasive tumor front, making an in-depth characterization of reticular fiber scaffolding, infiltrating immune cells, gene expression, and epigenetic profiles of classified aggressive primary uterine adenocarcinomas (24 patients) and leiomyosarcomas (11 patients). Sections of formalin-fixed samples before and after microdissection were scanned and studied. Reticular fiber architecture and immune cell infiltration were analyzed by automatized algorithms in colocalized regions of interest. Despite morphometric resemblance between reticular fibers and high presence of macrophages, we found some variance in other immune cell populations and distinctive gene expression and cell adhesion-related methylation signatures. Although no evident overall differences in immune response were detected at the gene expression and methylation level, impaired antimicrobial humoral response might be involved in uterine leiomyosarcoma spread. Similarities found at the invasive tumor front of uterine adenocarcinomas and leiomyosarcomas could facilitate the use of common biomarkers and therapies. Furthermore, molecular and architectural characterization of the invasive front of uterine malignancies may provide additional prognostic information beyond established prognostic factors.
侵袭性肿瘤前沿（肿瘤-宿主界面）在恶性细胞进展和转移中至关重要。肿瘤细胞与驻留和浸润的宿主细胞、周围的细胞外基质以及分泌因子之间的相互作用最终决定了肿瘤的命运。在此，我们聚焦于侵袭性肿瘤前沿，对24例侵袭性原发性子宫腺癌和11例平滑肌肉瘤进行了深入的网状纤维支架、浸润免疫细胞、基因表达及表观遗传特征分析。对显微切割前后的福尔马林固定样本切片进行扫描和研究。通过自动算法在共定位的感兴趣区域分析网状纤维结构和免疫细胞浸润情况。尽管网状纤维在形态测量上相似且巨噬细胞大量存在，但我们发现其他免疫细胞群体存在一些差异，以及独特的基因表达和细胞黏附相关的甲基化特征。虽然在基因表达和甲基化水平未检测到明显的整体免疫反应差异，但受损的抗微生物体液反应可能与子宫平滑肌肉瘤的扩散有关。在子宫腺癌和平滑肌肉瘤的侵袭性肿瘤前沿发现的相似性可能有助于使用共同的生物标志物和治疗方法。此外，子宫恶性肿瘤侵袭前沿的分子和结构特征可能提供超越既定预后因素的额外预后信息。
