Development of a Contacting Transwell Co-culture System for the Propagation of Primary Central Nervous System Lymphoma

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2023 Dec 13

PMID 38089883

Authors

Mayuko Nishi

Kensuke Tateishi

Jeremiah Stanleyraj Sundararaj

Yoko Ino

Yusuke Nakai

Yasuyoshi Hatayama

Yutaro Yamaoka

Yusaku Mihana

Kei Miyakawa

Hirokazu Kimura

Yayoi Kimura

Tetsuya Yamamoto

Akihide Ryo

Affiliations

Soon will be listed here.

Abstract

Primary central nervous system lymphoma (PCNSL) is a malignant neoplasm of the central nervous system that is refractory to treatment and has extremely poor prognosis. One factor hindering the development of therapeutic options for PCNSL is its molecular heterogeneity and the extreme difficulty in establishing cell lines that permit intensive research on this disease. In the present study, we developed a method to propagate PCNSL cells using a contacting transwell cell culture system involving brain vascular pericytes. The co-culture system was found to recapitulate the tumor microenvironment that is influenced by the biological activity of adjacent pericytes, and to sustain the survival and proliferation of PCNSL cells . We further delineated the underlying molecular mechanisms and found that the HGF-c-Met axis may be involved in the long-term culture of PCNSL cells. Moreover, the peptidylprolyl isomerase Pin1 was found to play a key role in PCNSL cell survival and it sustained proliferation through interactions with key transcription factors related to B-cell lymphomagenesis. These results suggest that our co-culture system is well suited to analyzing the biological and molecular characteristics of PCNSL, and may contribute to the discovery of new therapeutic interventions.

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