6533b860fe1ef96bd12c3965

RESEARCH PRODUCT

Characterizing the Invasive Tumor Front of Aggressive Uterine Adenocarcinoma and Leiomyosarcoma

Sabina SanegreSabina SanegreNúria EritjaNúria EritjaCarlos De AndreaCarlos De AndreaJuan Diaz-martinJuan Diaz-martinÁNgel Diaz-lagaresÁNgel Diaz-lagaresMaría Amalia JácomeCarmen Salguero-arandaCarmen Salguero-arandaDavid García RosBen DavidsonBen DavidsonRafel LopezRafel LopezRafel LopezIgnacio MeleroIgnacio MeleroSamuel NavarroSamuel NavarroSantiago Ramon Y CajalSantiago Ramon Y CajalEnrique De AlavaEnrique De AlavaXavier Matias-guiuXavier Matias-guiuRosa NogueraRosa Noguera

subject

LeiomyosarcomaReticular fiberreticular fibersÚter - TumorsQH301-705.5Músculs - Càncer:neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales femeninos::neoplasias uterinas [ENFERMEDADES]extracellular matrix:factores biológicos::biomarcadores::marcadores tumorales [COMPUESTOS QUÍMICOS Y DROGAS]:Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms Female::Uterine Neoplasms [DISEASES]BiologyMetastasisMetastasisCell and Developmental BiologyImmune system:neoplasias::neoplasias por tipo histológico::neoplasias de tejido conjuntivo y de tejidos blandos::neoplasias de tejido muscular::leiomiosarcoma [ENFERMEDADES]Càncer d'úterimmune cellsTumor-host interfaceMetàstasimedicineUterine cancer:Neoplasms::Neoplasms by Histologic Type::Neoplasms Connective and Soft Tissue::Neoplasms Muscle Tissue::Leiomyosarcoma [DISEASES]tumor microenvironment:Biological Factors::Biomarkers::Biomarkers Tumor [CHEMICALS AND DRUGS]Biology (General)epigenetic profilesMicrodissectionAntimicrobial humoral responseOriginal ResearchTumor microenvironmentMarcadors tumoralsImmune cellsEpigenetic profilesCell BiologyExtracellular matrixmedicine.diseaseEpigenèticaTumor microenvironmentReticular connective tissueCancer researchgene expressionEpigeneticsGene expressionThis is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY)Reticular fiberstumor-host interfaceDevelopmental Biology

description

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.

10.3389/fcell.2021.670185https://www.frontiersin.org/articles/10.3389/fcell.2021.670185/full