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

Delle Cave, D.; Buonaiuto, S.; Mangini, M.; Sainz, B.; Di Domenico, A.; Teresa Iavazzo, T.; Andolfi, G.; Cortina Duran, C.; Sevillano, M.; Heeschen, C.; Colonna, V.; Corona, M.; Cucciardi, A.; Di Guida, M.; Batlle, E.; De Luca, A.; Lonardo, E.

doi:10.1101/2022.03.24.485651

bioRxiv · 10.1101/2022.03.24.485651

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

Delle Cave, D.·Buonaiuto, S.·Mangini, M.·Sainz, B.·Di Domenico, A.·Teresa Iavazzo, T.·Andolfi, G.·Cortina Duran, C.·Sevillano, M.·Heeschen, C.·Colonna, V.·Corona, M.·Cucciardi, A.·Di Guida, M.·Batlle, E.·De Luca, A.·Lonardo, E.

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Abstract

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-{beta} signaling pathway. Treatment with Vactosertib, a new small molecule inhibitor of transforming growth factor-{beta} (TGF-{beta}) 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.

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Delle Cave, D., Buonaiuto, S., Mangini, M., Sainz, B., Di Domenico, A., Teresa Iavazzo, T., Andolfi, G., Cortina Duran, C., Sevillano, M., Heeschen, C., Colonna, V., Corona, M., Cucciardi, A., Di Guida, M., Batlle, E., De Luca, A., Lonardo, E.. 2022-03-27. LAMC2 marks a tumor-initiating cell population with an aggressive signature in pancreatic cancer. https://doi.org/10.1101/2022.03.24.485651

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