Biomimetic Approach of Brain Vasculature Rapidly Characterizes Inter‐ and Intra‐Patient Migratory Diversity of Glioblastoma

Author:

Crestani Michele12,Kakogiannos Nikolaos13,Iori Simone1,Iannelli Fabio14,Dini Tania1,Maderna Claudio1,Giannotta Monica1,Pelicci Giuliana45,Maiuri Paolo16,Monzo Pascale1ORCID,Gauthier Nils C.1

Affiliation:

1. IFOM ETS – The AIRC Institute of Molecular Oncology Via Adamello 16 Milan 20139 Italy

2. Laboratory of Applied Mechanobiology Department of Health Sciences and Technology Institute of Translational Medicine ETH Zurich Zurich CH‐8093 Switzerland

3. Institute of Immunology Biomedical Sciences Research Centre “Alexander Fleming” 34 Fleming Street Vari 16672 Greece

4. Department of Experimental Oncology IEO European Institute of Oncology IRCCS Milan 20139 Italy

5. Department of Translational Medicine Piemonte Orientale University ‘‘Amedeo Avogadro’’ Novara 28100 Italy

6. Dipartimento di Medicina Molecolare e Biotecnologie Mediche Università degli Studi di Napoli Federico II Via S. Pansini 5 Naples 80131 Italy

Abstract

AbstractGlioblastomas exhibit remarkable heterogeneity at various levels, including motility modes and mechanoproperties that contribute to tumor resistance and recurrence. In a recent study using gridded micropatterns mimicking the brain vasculature, glioblastoma cell motility modes, mechanical properties, formin content, and substrate chemistry are linked. Now is presented, SP2G (SPheroid SPreading on Grids), an analytic platform designed to identify the migratory modes of patient‐derived glioblastoma cells and rapidly pinpoint the most invasive sub‐populations. Tumorspheres are imaged as they spread on gridded micropatterns and analyzed by this semi‐automated, open‐source, Fiji macro suite that characterizes migration modes accurately. SP2G can reveal intra‐patient motility heterogeneity with molecular correlations to specific integrins and EMT markers. This system presents a versatile and potentially pan‐cancer workflow to detect diverse invasive tumor sub‐populations in patient‐derived specimens and offers a valuable tool for therapeutic evaluations at the individual patient level.

Funder

Fondazione AIRC per la ricerca sul cancro ETS

Publisher

Wiley

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