Noninvasive morpho-molecular imaging reveals early therapy-induced senescence in human cancer cells

Author:

Bresci Arianna1ORCID,Kim Jeong Hee2ORCID,Ghislanzoni Silvia3ORCID,Manetti Francesco1ORCID,Wu Lintong2ORCID,Vernuccio Federico1ORCID,Ceconello Chiara1ORCID,Sorrentino Salvatore1ORCID,Barman Ishan245ORCID,Bongarzone Italia3ORCID,Cerullo Giulio16ORCID,Vanna Renzo6ORCID,Polli Dario16ORCID

Affiliation:

1. Department of Physics, Politecnico di Milano, Milan, Italy.

2. Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, USA.

3. Department of Advanced Diagnostics, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.

4. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

5. The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

6. CNR-Institute for Photonics and Nanotechnologies (CNR-IFN), Milan, Italy.

Abstract

Anticancer therapy screening in vitro identifies additional treatments and improves clinical outcomes. Systematically, although most tested cells respond to cues with apoptosis, an appreciable portion enters a senescent state, a critical condition potentially driving tumor resistance and relapse. Conventional screening protocols would strongly benefit from prompt identification and monitoring of therapy-induced senescent (TIS) cells in their native form. We combined complementary all-optical, label-free, and quantitative microscopy techniques, based on coherent Raman scattering, multiphoton absorption, and interferometry, to explore the early onset and progression of this phenotype, which has been understudied in unperturbed conditions. We identified TIS manifestations as early as 24 hours following treatment, consisting of substantial mitochondrial rearrangement and increase of volume and dry mass, followed by accumulation of lipid vesicles starting at 72 hours. This work holds the potential to affect anticancer treatment research, by offering a label-free, rapid, and accurate method to identify initial TIS in tumor cells.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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