LAMC2 marks a tumor-initiating cell population with an aggressive signature in pancreatic cancer

• Published in: bioRxiv
• Main Authors: Donatella Delle Cave, Buonaiuto, Silvia, Mangini, Maria, Sainz, Bruno, Annalisa Di Domenico, Iavazzo, Tea Teresa, Andolfi, Gennaro, Carme Cortina Duran, Sevillano, Marta, Heeschen, Christopher, Colonna, Vincenza, Corona, Marco, Cucciardi, Antonio, Martina Di Guida, Batlle, Eduard, Annachiara De Luca, Lonardo, Enza
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 27.03.2022; Cold Spring Harbor Laboratory
• Edition: 1.1
• Subjects: Activin; Cancer Biology; Cell self-renewal; Metastases; Metastasis; mRNA; Pancreatic cancer; Population studies; Signal transduction; Stem cells; Therapeutic targets; Transforming growth factor-b; Laminin γ2 (LAMC2); Tumor-initiating cells (TICs); Pancreatic ductal adenocarcinoma (PDAC); Vactosertib; TGF-β signaling
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/2022.03.24.485651

Tumor-initiating cells (TIC), also known as cancer stem cells, are considered a specific subpopulation of cells necessary for cancer initiation and metastasis. Here, we report a LAMC2-positive cell population, which is endowed with enhanced self-renewal capacity, and is sufficient for tumor initiation, differentiation, and driving metastasis. Mechanistically, mRNA profiling of these cells indicate a prominent squamous signature, and differentially activated pathways critical for tumor growth and metastasis, including deregulation of the TGF-β signaling pathway. Treatment with Vactosertib, a new small molecule inhibitor of transforming growth factor-β (TGF-β) type I receptor (activin receptor-like kinase-5, ALK5), completely abrogated the lung metastasis, primarily originating from LAMC2 expressing cells. Our results prompt further study of this TIC population in pancreatic cancer and exploration as a potential therapeutic target and/or biomarker. Competing Interest Statement The authors have declared no competing interest.