TY - JOUR
T1 - Tumor cell heterogeneity and its transcriptional bases in pancreatic cancer
T2 - a tale of two cell types and their many variants
AU - Milan, Marta
AU - Diaferia, Giuseppe R.
AU - Natoli, Gioacchino
N1 - Funding Information:
Research on PDAC in GN laboratory is supported by AIRC (Associazione Italiana Ricerca sul Cancro, AIRC Investigator Grant 20251 and AIRC 5x1000 Grant ISM) and partially by the Italian Ministry of Health with “Ricerca Corrente” and 5x1000 funds. GRD is supported by the Italian Ministry of Health (grant GR‐2016‐02361721 to G.R.D). Marta Milan is a recipient of a long‐term fellowship from AIRC.
Publisher Copyright:
© 2021 The Authors
PY - 2021/7/1
Y1 - 2021/7/1
N2 - Pancreatic ductal adenocarcinoma (PDAC), one of the most highly lethal tumors, is characterized by complex histology, with a massive fibrotic stroma in which both pseudo-glandular structures and compact nests of abnormally differentiated tumor cells are embedded, in different proportions and with different mutual relationships in space. This complexity and the heterogeneity of the tumor component have hindered the development of a broadly accepted, clinically actionable classification of PDACs, either on a morphological or a molecular basis. Here, we discuss evidence suggesting that such heterogeneity can to a large extent, albeit not exclusively, be traced back to two main classes of PDAC cells that commonly coexist in the same tumor: cells that maintained their ability to differentiate toward endodermal, mucin-producing epithelia and epithelial cells unable to form glandular structures and instead characterized by various levels of squamous differentiation and the expression of mesenchymal lineage genes. The underlying gene regulatory networks and how they are controlled by distinct transcription factors, as well as the practical implications of these two different populations of tumor cells, are discussed.
AB - Pancreatic ductal adenocarcinoma (PDAC), one of the most highly lethal tumors, is characterized by complex histology, with a massive fibrotic stroma in which both pseudo-glandular structures and compact nests of abnormally differentiated tumor cells are embedded, in different proportions and with different mutual relationships in space. This complexity and the heterogeneity of the tumor component have hindered the development of a broadly accepted, clinically actionable classification of PDACs, either on a morphological or a molecular basis. Here, we discuss evidence suggesting that such heterogeneity can to a large extent, albeit not exclusively, be traced back to two main classes of PDAC cells that commonly coexist in the same tumor: cells that maintained their ability to differentiate toward endodermal, mucin-producing epithelia and epithelial cells unable to form glandular structures and instead characterized by various levels of squamous differentiation and the expression of mesenchymal lineage genes. The underlying gene regulatory networks and how they are controlled by distinct transcription factors, as well as the practical implications of these two different populations of tumor cells, are discussed.
KW - differentiation
KW - pancreatic cancer
KW - pancreatic ductal adenocarcinoma
KW - transcription
KW - tumor grading
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U2 - 10.15252/embj.2020107206
DO - 10.15252/embj.2020107206
M3 - Review article
C2 - 33844319
AN - SCOPUS:85104127429
VL - 40
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 13
M1 - e107206
ER -