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Supplementary Figure 2 from Tumor-Induced Pressure in the Bone Microenvironment Causes Osteocytes to Promote the Growth of Prostate Cancer Bone Metastases

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posted on 2023-03-30, 23:06 authored by Joseph L. Sottnik, Jinlu Dai, Honglai Zhang, Brittany Campbell, Evan T. Keller

Supplementary Figure 2: MLO-Y4 CM promotes PCa viability, migration, and invasion. CM was isolated from MLO-Y4 cells. Viability of PCa cells after 24 hour incubation with MLO-Y4 CM as measured by resazurin. Student's two-tailed unpaired t-test was used to assess statistical differences; p<0.05. CM was also used as a chemoattractant in Boyden chamber assays to assess PCa migration and invasion. CM was compared to negative control (RPMI with 0.1% FBS) and positive control (RPMI with 10% FBS) media. One-way ANOVA with Bonferroni post-test used for analysis; bars represent significant differences where p<0.05.

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ARTICLE ABSTRACT

Cross-talk between tumor cells and their microenvironment is critical for malignant progression. Cross-talk mediators, including soluble factors and direct cell contact, have been identified, but roles for the interaction of physical forces between tumor cells and the bone microenvironment have not been described. Here, we report preclinical evidence that tumor-generated pressure acts to modify the bone microenvironment to promote the growth of prostate cancer bone metastases. Tumors growing in mouse tibiae increased intraosseous pressure. Application of pressure to osteocytes, the main mechanotransducing cells in bone, induced prostate cancer growth and invasion. Mechanistic investigations revealed that this process was mediated in part by upregulation of CCL5 and matrix metalloproteinases in osteocytes. Our results defined the critical contribution of physical forces to tumor cell growth in the tumor microenvironment, and they identified osteocytes as a critical mediator in the bone metastatic niche. Cancer Res; 75(11); 2151–8. ©2015 AACR.

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