ISSN: 1449-2288International Journal of Biological Sciences
Global reach, higher impact
Int J Biol Sci 2022; 18(4):1677-1694. doi:10.7150/ijbs.69178 This issue Cite
Research Paper
TSG-6 promotes Cancer Cell aggressiveness in a CD44-Dependent Manner and Reprograms Normal Fibroblasts to create a Pro-metastatic Microenvironment in Colorectal Cancer
Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510655, China.
*The authors contributed equally to this work.
Citation:
Liu B, Liu T, Liu Y, Feng X, Jiang X, Long J, Ye S, Chen D, Wang J, Yang Z. TSG-6 promotes Cancer Cell aggressiveness in a CD44-Dependent Manner and Reprograms Normal Fibroblasts to create a Pro-metastatic Microenvironment in Colorectal Cancer. Int J Biol Sci 2022; 18(4):1677-1694. doi:10.7150/ijbs.69178. https://www.ijbs.com/v18p1677.htm
Other stylesAbstract
Tumor necrosis factor α stimulated gene 6 (TSG-6), a 30-KD secretory protein, plays an essential role in modulating inflammatory responses and extracellular matrix remodeling. However, little is known regarding the role of TSG-6 in human cancers. Here, we investigated the mechanism of action and the role of TSG-6 in colorectal cancer (CRC) metastasis. We found that TSG-6 was highly expressed in tumor tissues and was associated with poor prognosis and metastasis in CRC. Mechanistically, TSG-6 overexpression in CRC cells resulted in ERK activation and epithelial-mesenchymal transition by means of stabilizing CD44 and facilitating the CD44-EGFR complex formation on the cell membrane. Consequently, this resulted in the promotion of tumor migration and invasion both in vitro and in vivo. Notably, our data showed that CRC cells secreted TSG-6 could trigger a paracrine activation of JAK2-STAT3 signaling and reprogram normal fibroblasts into cancer-associated fibroblasts, which exhibited upregulation of pro-metastatic cytokines (CCL5 and MMP3) and higher movement ability. In animal models, the co-injection of cancer cells and TSG6-reprogrammed fibroblasts led to a significant increase in tumor metastasis. Our findings indicated that TSG-6 overexpression in CRC cells could promote cancer metastasis in both an autocrine and paracrine manner. Therefore, targeting TSG-6 might be a potential therapeutic strategy for the treatment of metastatic CRC.
Keywords: TSG-6, Fibroblast, Colorectal Cancer, Metastasis
Citation styles
APA
Liu, B., Liu, T., Liu, Y., Feng, X., Jiang, X., Long, J., Ye, S., Chen, D., Wang, J., Yang, Z. (2022). TSG-6 promotes Cancer Cell aggressiveness in a CD44-Dependent Manner and Reprograms Normal Fibroblasts to create a Pro-metastatic Microenvironment in Colorectal Cancer. International Journal of Biological Sciences, 18(4), 1677-1694. https://doi.org/10.7150/ijbs.69178.
ACS
Liu, B.; Liu, T.; Liu, Y.; Feng, X.; Jiang, X.; Long, J.; Ye, S.; Chen, D.; Wang, J.; Yang, Z. TSG-6 promotes Cancer Cell aggressiveness in a CD44-Dependent Manner and Reprograms Normal Fibroblasts to create a Pro-metastatic Microenvironment in Colorectal Cancer. Int. J. Biol. Sci. 2022, 18 (4), 1677-1694. DOI: 10.7150/ijbs.69178.
NLM
Liu B, Liu T, Liu Y, Feng X, Jiang X, Long J, Ye S, Chen D, Wang J, Yang Z. TSG-6 promotes Cancer Cell aggressiveness in a CD44-Dependent Manner and Reprograms Normal Fibroblasts to create a Pro-metastatic Microenvironment in Colorectal Cancer. Int J Biol Sci 2022; 18(4):1677-1694. doi:10.7150/ijbs.69178. https://www.ijbs.com/v18p1677.htm
CSE
Liu B, Liu T, Liu Y, Feng X, Jiang X, Long J, Ye S, Chen D, Wang J, Yang Z. 2022. TSG-6 promotes Cancer Cell aggressiveness in a CD44-Dependent Manner and Reprograms Normal Fibroblasts to create a Pro-metastatic Microenvironment in Colorectal Cancer. Int J Biol Sci. 18(4):1677-1694.
This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.