Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. PDAC is characterized by a complex tumor microenvironment (TME), that plays a pivotal role in disease progression and resistance to therapy. Investigating the spatial distribution and interaction of TME cells with the tumor is the basis for understanding the mechanisms underlying disease progression and represents a current challenge in PDAC research. Imaging mass cytometry (IMC) is the major multiplex imaging technology for the spatial analysis of tumor heterogeneity. However, there is a dearth of reports of multiplexed IMC panels for different preclinical mouse models, including pancreatic cancer. We addressed this gap by utilizing two preclinical models of PDAC: the genetically engineered, bearing KRAS–TP53 mutations in pancreatic cells, and the orthotopic, and developed a 28–marker panel for single–cell IMC analysis to assess the abundance, distribution and phenotypes of cells involved in PDAC progression and their reciprocal functional interactions. Herein, we provide an unprecedented definition of the distribution of TME cells in PDAC and compare the diversity between transplanted and genetic disease models. The results obtained represent an important and customizable tool for unraveling the complexities of PDAC and deciphering the mechanisms behind therapy resistance.

Multiplexed Imaging Mass Cytometry Analysis in Preclinical Models of Pancreatic Cancer / M. Erreni, M.R. Fumagalli, D. Zanini, E. Candiello, G. Tiberi, R. Parente, R. D’Anna, E. Magrini, F. Marchesi, P. Cappello, A. Doni. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 25:3(2024), pp. 1389.1-1389.21. [10.3390/ijms25031389]

Multiplexed Imaging Mass Cytometry Analysis in Preclinical Models of Pancreatic Cancer

M. Erreni
;
M.R. Fumagalli;R. D’Anna;F. Marchesi;
2024

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. PDAC is characterized by a complex tumor microenvironment (TME), that plays a pivotal role in disease progression and resistance to therapy. Investigating the spatial distribution and interaction of TME cells with the tumor is the basis for understanding the mechanisms underlying disease progression and represents a current challenge in PDAC research. Imaging mass cytometry (IMC) is the major multiplex imaging technology for the spatial analysis of tumor heterogeneity. However, there is a dearth of reports of multiplexed IMC panels for different preclinical mouse models, including pancreatic cancer. We addressed this gap by utilizing two preclinical models of PDAC: the genetically engineered, bearing KRAS–TP53 mutations in pancreatic cells, and the orthotopic, and developed a 28–marker panel for single–cell IMC analysis to assess the abundance, distribution and phenotypes of cells involved in PDAC progression and their reciprocal functional interactions. Herein, we provide an unprecedented definition of the distribution of TME cells in PDAC and compare the diversity between transplanted and genetic disease models. The results obtained represent an important and customizable tool for unraveling the complexities of PDAC and deciphering the mechanisms behind therapy resistance.
imaging mass cytometry; multiplexed imaging; pancreatic cancer; PDAC; preclinical models
Settore MED/04 - Patologia Generale
2024
Article (author)
File in questo prodotto:
File Dimensione Formato  
ijms-25-01389-v2_compressed.pdf

accesso aperto

Descrizione: Article
Tipologia: Publisher's version/PDF
Dimensione 1.94 MB
Formato Adobe PDF
1.94 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1026173
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 0
social impact