Frontiers in Cell and Developmental Biology (Jun 2021)

Characterizing the Invasive Tumor Front of Aggressive Uterine Adenocarcinoma and Leiomyosarcoma

  • Sabina Sanegre,
  • Sabina Sanegre,
  • Núria Eritja,
  • Núria Eritja,
  • Carlos de Andrea,
  • Carlos de Andrea,
  • Juan Diaz-Martin,
  • Juan Diaz-Martin,
  • Ángel Diaz-Lagares,
  • Ángel Diaz-Lagares,
  • María Amalia Jácome,
  • Carmen Salguero-Aranda,
  • Carmen Salguero-Aranda,
  • David García Ros,
  • Ben Davidson,
  • Ben Davidson,
  • Rafel Lopez,
  • Rafel Lopez,
  • Rafel Lopez,
  • Ignacio Melero,
  • Ignacio Melero,
  • Samuel Navarro,
  • Samuel Navarro,
  • Santiago Ramon y Cajal,
  • Santiago Ramon y Cajal,
  • Enrique de Alava,
  • Enrique de Alava,
  • Xavier Matias-Guiu,
  • Xavier Matias-Guiu,
  • Rosa Noguera,
  • Rosa Noguera

DOI
https://doi.org/10.3389/fcell.2021.670185
Journal volume & issue
Vol. 9

Abstract

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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.

Keywords