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Wnt/β-Catenin Signaling Pathway Regulates Osteogenesis for Breast Cancer Bone Metastasis: Experiments in an In Vitro Nanoclay Scaffold Cancer Testbed
journal contribution
posted on 2019-11-13, 18:37 authored by Sumanta Kar, Haneesh Jasuja, Dinesh R. Katti, Kalpana S. KattiBreast cancer shows a high affinity toward bone, causing
bone-related
complications, leading to a poor clinical prognosis. The Wnt/β-catenin
signaling pathway has been well-documented for the bone regenerative
process; however, the regulation of the Wnt/β-catenin pathway
in breast cancer bone metastasis is poorly explored. Here, we report
that the Wnt/β-catenin signaling pathway has a significant effect
on osteogenesis during breast cancer bone metastasis. In this study,
we have created a 3D in vitro breast cancer bone
metastatic microenvironment using nanoclay-based scaffolds along with
osteogenically differentiated human mesenchymal stem cells (MSCs)
and human breast cancer cells (MCF-7 and MDA-MB-231). The results
showed upregulation in expressions of Wnt-related factors (Wnt-5a,
β-catenin, AXIN2, and LRP5) in sequential cultures of MSCs with
MCF-7 as compared to sequential cultures of MSCs with MDA-MB-231.
Sequential cultures of MSCs with MCF-7 also showed higher β-catenin
expression on the protein levels than sequential cultures of MSCs
with MDA-MB-231. Stimulation of Wnt/β-catenin signaling in sequential
cultures of MSCs with MCF-7 by ET-1 resulted in increased bone formation,
whereas inactivation of Wnt/β-catenin signaling by DKK-1 displayed
a significant decrease in bone formation, mimicking bone lesions in
breast cancer patients. These data collectively demonstrate that Wnt/β-catenin
signaling governs osteogenesis within the tumor-harboring bone microenvironment,
leading to bone metastasis. The nanoclay scaffold provides a unique
testbed approach for analysis of the pathways of cancer metastasis.
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AXINDKKsequential culturestumor-harboring bone microenvironmentbone formationMDA-MB -231. StimulationETLRPVitro Nanoclay Scaffold Cancer Testbed Breast cancerbreast cancer cellsbreast cancer bone metastasisWnt -5a β- cateninbone regenerative processMDA-MB -231. Sequential culturesβ- catenin expressionbreast cancer bone metastatic microenvironmentbreast cancer patientsMCF -7MSCpathwayBreast Cancer Bone Metastasis
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