Int J Biol Sci 2022; 18(13):5038-5055. doi:10.7150/ijbs.70083 This issue

Research Paper

Tsp2 Facilitates Tumor-associated Fibroblasts Formation and Promotes Tumor Progression in Retroperitoneal Liposarcoma

Chang Xu1, Liang Yan1, Xiaoya Guan1, Zhen Wang1, Jianhui Wu1, Ang Lv1, Daoning Liu1, Faqiang Liu1, Bin Dong2, Min Zhao3, Ling Jia3, Xiuyun Tian1✉, Chunyi Hao1✉

1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & Institute, Beijing, China.
2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Central Laboratory, Peking University Cancer Hospital & Institute, Beijing, China.
3. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China.

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Citation:
Xu C, Yan L, Guan X, Wang Z, Wu J, Lv A, Liu D, Liu F, Dong B, Zhao M, Jia L, Tian X, Hao C. Tsp2 Facilitates Tumor-associated Fibroblasts Formation and Promotes Tumor Progression in Retroperitoneal Liposarcoma. Int J Biol Sci 2022; 18(13):5038-5055. doi:10.7150/ijbs.70083. Available from https://www.ijbs.com/v18p5038.htm

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Abstract

Graphic abstract

Retroperitoneal liposarcoma (RLPS) is the most common subtype of retroperitoneal soft tissue sarcoma, characterized by a high recurrence rate and insensitivity to radiotherapy and chemotherapy. The function of tumor microenvironmental components, especially tumor-associated fibroblasts (TAFs), remains unclear in RLPS. The crosstalk between tumor cells and stromal cells should be clarified for therapy target discovery in RLPS. In this study, we demonstrated that TAFs from dedifferentiated liposarcoma (DDLPS) could attract LPS cells and promote their proliferation and migration. However, although α-SMA is positively expressed in RLPS, its expression does not indicate prognosis. By screening differentially expressed genes, performing Oncomine visualization, TCGA gene expression correlation analysis and qPCR verification, we determined that thrombospondin-2 (THBS2) gene expression was related to TAFs. The expression of Tsp2 protein, which was encoded by THBS2, was correlated with α-SMA expression, and it was an independent predictive factor for disease-free survival and recurrence-free survival in patients with RLPS. In vitro, Tsp2 facilitated the transformation of bone marrow-derived fibroblasts (BMFs) to TAFs and promoted the malignant biological behaviors of LPS cells by activating the MAPK/MEK/ERK pathway. Therefore, suppression of Tsp2 is expected to be a promising treatment method for RLPS patients.

Keywords: retroperitoneal liposarcoma, Tsp2, tumor-associated fibroblasts, tumor microenvironment, tumor progression