Crosstalk between macrophages and myxoid liposarcoma cells increases spreading and invasiveness of tumor cells

Michele Minopoli, Sabrina Sarno, Lucia Cannella, Salvatore Tafuto, Gosuè Scognamiglio, Michele Gallo, Flavio Fazioli, Rosa Azzaro, Gaetano Apice, Biagio De Angelis, Elena Tamborini, Cecilia Garofalo, Ymera Pignochino, Laura Mercatali, Toni Ibrahim, Rita Falcioni, Beatrice Valenti, Roberta Maestro, Katia Scotlandi, Annarosaria De ChiaraMaria Vincenza Carriero

Research output: Contribution to journalArticlepeer-review

Abstract

Myxoid liposarcoma (MLPS) is the second most common subtype of liposarcoma and has tendency to metastasize to soft tissues. To date, the mechanisms of invasion and metastasis of MLPS remain unclear, and new therapeutic strategies that improve patients' outcomes are expected. In this study, we analyzed by immunohistochemistry the immune cellular components and mi-crovessel density in tumor tissues from patients affected by MLPS. In order to evaluate the effects of primary human MLPS cells on macrophage polarization and, in turn, the ability of macrophages to influence invasiveness of MLPS cells, non-contact and 3D organotypic co-cultures were set up. High grade MLPS tissues were found heavily vascularized, exhibited a CD3, CD4, and CD8 positive T lymphocyte-poor phenotype and were massively infiltrated by CD163 positive M2-like macro-phages. Conversely, low grade MLPS tissues were infiltrated by a discrete amount of CD3, CD4, and CD8 positive T lymphocytes and a scarce amount of CD163 positive macrophages. Kaplan– Meier analysis revealed a shorter Progression Free Survival in MLPS patients whose tumor tissues were highly vascularized and heavily infiltrated by CD163 positive macrophages, indicating a clear-cut link between M2-like macrophage abundance and poor prognosis in patients. Moreover, we documented that, in co-culture, soluble factors produced by primary human MLPS cells induce macrophage polarization toward an M2-like phenotype which, in turn, increases MLPS cell capabil-ity to spread into extracellular matrix and to cross endothelial monolayers. The identification of M2-like polarization factors secreted by MLPS cells may allow to develop novel targeted therapies coun-teracting MLPS progression.

Original languageEnglish
Article number3298
JournalCancers
Volume13
Issue number13
DOIs
Publication statusPublished - Jul 1 2021

Keywords

  • Myxoid liposarcoma
  • Tumor associated macrophages
  • Tumor microenvironment
  • Tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Crosstalk between macrophages and myxoid liposarcoma cells increases spreading and invasiveness of tumor cells'. Together they form a unique fingerprint.

Cite this