Depleting RhoA/Stress Fiber-Organized Fibronectin Matrices on Tumor Cells Non-Autonomously Aggravates Fibroblast-Driven Tumor Cell Growth

• Main Authors: Li-Tzu Huang, Chen-Lung Tsai, Shin-Huei Huang, Ming-Min Chang, Wen-Tsan Chang, Li-Hsin Cheng, Hung-Chi Cheng
• Format: Article
• Language: English
• Published: MDPI AG 2020-11-01
• Series: International Journal of Molecular Sciences
• Subjects: Fibronectin (FN); pericellular FN matrices; actin stress fiber cytoskeleton; RhoA; tumor microenvironments; cancer associated fibroblasts
• Online Access: https://www.mdpi.com/1422-0067/21/21/8272

Fibronectin (FN) expressed by tumor cells has been known to be tumor suppressive but the pericellular FN (periFN) assembled on circulating tumor cells appears to evidently promote distant metastasis. Whereas the regulation of periFN assembly in suspended cells has currently been under investigation, how it is regulated in adherent tumor cells and the role of periFN in primary tumor growth remain elusive. Techniques of RNAi, plasmid transfections, immunoblotting, fluorescence/immunohistochemistry staining, cell proliferation assays, and primary tumor growth in C57BL6 mice and Fischer 344 rats were employed in this study. We found that endogenously synthesized FN in adherent tumor cells was required for periFN assembly which was aligned by RhoA-organized actin stress fiber (SF). Depleting periFN on adherent tumor cells congruently promoted in vivo tumor growth but surprisingly did not autonomously impact on in vitro tumor cell proliferation and apoptosis, suggestive of a non-autonomous role of periFN in in vivo tumor growth. We showed that the proliferative ability of shFN-expressing tumor cells was higher than shScramble cells did in the presence of fibroblasts. Altogether, these results suggested that depriving RhoA/SF-regulated periFN matrices non-autonomously promotes fibroblast-mediated tumor cell growth.