Combining organotypic tissue culture with light‐sheet microscopy (OTCxLSFM) to study glioma invasion.

Autor: Haydo, Alicia, Wehle, Andrej, Herold‐Mende, Christel, Kögel, Donat, Pampaloni, Francesco, Linder, Benedikt
Zdroj: EMBO Reports; 12/6/2023, Vol. 24 Issue 12, p1-16, 16p
Abstrakt: Glioblastoma is a very aggressive tumor and represents the most common primary brain malignancy. Key characteristics include its high resistance against conventional treatments, such as radio‐ and chemotherapy and its diffuse tissue infiltration, preventing complete surgical resection. The analysis of migration and invasion processes in a physiological microenvironment allows for enhanced understanding of these phenomena and can lead to improved therapeutic approaches. Here, we combine two state‐of‐the‐art techniques, adult organotypic brain tissue slice culture (OTC) and light‐sheet fluorescence microscopy (LSFM) of cleared tissues in a combined method termed OTCxLSFM. Using this methodology, we can show that glioblastoma tissue infiltration can be effectively blocked through treatment with arsenic trioxide or WP1066, as well as genetic depletion of the tetraspanin, transmembrane receptor CD9, or signal transducer and activator of transcription 3 (STAT3). With our analysis pipeline, we gain single‐cell level, three‐dimensional information, as well as insights into the morphological appearance of the tumor cells. Synopsis: Glioblastoma, an aggressive brain tumor, is resistant to standard treatments and infiltrates brain tissue. OTCxLSFM reveals that blocking infiltration is possible through pharmacological and genetic interventions, providing insights into tumor cell behavior.Glioblastoma is a primary brain malignancy known for its aggressiveness and resistance to conventional therapies.A novel approach, OTCxLSFM, combines brain tissue culture and advanced microscopy to study glioblastoma infiltration.Glioblastoma tissue infiltration is effectively blocked with arsenic trioxide and WP1066, or by targeting CD9 or STAT3.OTCxLSFM provides detailed single‐cell level, three‐dimensional insights into tumor cell behavior and morphology. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index