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  • Polymer Thin Film Promotes Tumor Spheroid Formation via JAK2-STAT3 Signaling Primed by Fibronectin-Integrin α5 and Sustained by LMO2-LDB1 Complex.

Polymer Thin Film Promotes Tumor Spheroid Formation via JAK2-STAT3 Signaling Primed by Fibronectin-Integrin α5 and Sustained by LMO2-LDB1 Complex.

Biomedicines (2022-11-12)
Sunyoung Seo, Nayoung Hong, Junhyuk Song, Dohyeon Kim, Yoonjung Choi, Daeyoup Lee, Sangyong Jon, Hyunggee Kim
ABSTRACT

Cancer stem-like cells (CSCs) are considered promising targets for anti-cancer therapy owing to their role in tumor progression. Extensive research is, therefore, being carried out on CSCs to identify potential targets for anti-cancer therapy. However, this requires the availability of patient-derived CSCs ex vivo, which remains restricted due to the low availability and diversity of CSCs. To address this limitation, a functional polymer thin-film (PTF) platform was invented to induce the transformation of cancer cells into tumorigenic spheroids. In this study, we demonstrated the functionality of a new PTF, polymer X, using a streamlined production process. Polymer X induced the formation of tumor spheroids with properties of CSCs, as revealed through the upregulated expression of CSC-related genes. Signal transducer and activator of transcription 3 (STAT3) phosphorylation in the cancer cells cultured on polymer X was upregulated by the fibronectin-integrin α5-Janus kinase 2 (JAK2) axis and maintained by the cytosolic LMO2/LBD1 complex. In addition, STAT3 signaling was critical in spheroid formation on polymer X. Our PTF platform allows the efficient generation of tumor spheroids from cancer cells, thereby overcoming the existing limitations of cancer research.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Nifuroxazide, A cell-permeable and orally available nitrofuran-based antidiarrheal agent that effectively suppresses the activation of cellular STAT1/3/5 transcription activity.
Millipore
JAK Inhibitor I, JAK Inhibitor I, CAS 457081-03-7, is a potent, reversible, cell-permeable, and ATP-competitive inhibitor of JAK 1 (IC₅₀ = 15 nM), JAK2 (IC₅₀ = 1 nM), JAK3 (Ki = 5 nM) and Tyk2 (IC₅₀ = 1 nM).
Sigma-Aldrich
Anti-α-Tubulin antibody, Mouse monoclonal, clone DM1A, purified from hybridoma cell culture