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Tumor cell-derived SPON2 promotes M2-polarized tumor-associated macrophage infiltration and cancer progression by activating PYK2 in CRC.

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收录情况： ◇ SCIE

作者：
Huang Chengmei[1,2,3] * ; Ou Ruizhang[1,2,3] * ; Chen Xiaoning[1,2,3] * ; Zhang Yaxin[1,2,3] ; Li Jiexi[4] ; Liang Yihao[5] ; Zhu Xiaohui[1,2,3] ; Liu Lei[1,2,3] ; Li Mingzhou[1,2,3] ; Lin Dagui[6] ; Qiu Junfeng[1,2,3] ; Liu Guanglong[1,2,3] ; Zhang Lingjie[1,2,3] ; Wu Yuanyuan[1,2,3] ; Tang Huiyi[7] ; Liu Yanmin[6] ; Liang Li[1,2,3] ; Ding Yanqing[1,2,3] ; Liao Wenting[1,2,3,6] ;
机构： [1]Department of Pathology, Nanfang Hospital, Southern Medical University,Guangzhou 510515, Guangdong, China [2]Department of Pathology, Schoolof Basic Medical Sciences, Southern Medical University, Guangzhou 510515,China [3]Guangdong Provincial Key Laboratory of Molecular Tumor Pathology,Guangzhou, Guangdong, China [4]Department of Cancer Biology, The Universityof Texas MD Anderson Cancer Center, Houston, TX 77030, USA [5]Departmentof Orthopedist, Guangdong Provincial Hospital of Chinese Medicine,Guangzhou 510000, China [6]State Key Laboratory of Oncology in South China,Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen UniversityCancer Center, Guangzhou, China [7]Department of Histology and Embryology,School of Basic Medical Sciences, Southern Medical University, Guangzhou510515, China
出处：
DOI： 10.1186/s13046-021-02108-0
ISSN：

摘要：
Tumor-associated macrophages (TAMs) are key regulators of the complex interplay between cancer and the immune microenvironment. Tumor cell-derived spondin 2 (SPON2) is an extracellular matrix glycoprotein that has complicated roles in recruitment of macrophages and neutrophils during inflammation. Overexpression of SPON2 has been shown to promote tumor cell migration in colorectal cancer (CRC). However, the mechanism by which SPON2 regulates the accumulation of TAMs in the tumor microenvironment (TME) of CRC is unknown.Immunohistochemistry was used to examine SPON2 expression in clinical CRC tissues. In vitro migration assays, transendothelial migration assays (iTEM), and cell adhesion assays were used to investigate the effects of SPON2 on monocyte/macrophage migration. Subcutaneous tumor formation and orthotopic implantation assays were performed in C57 BL/6 mice to confirm the effects of SPON2 on TAM infiltration in tumors.SPON2 expression is positively correlated with M2-TAM infiltration in clinical CRC tumors and poor prognosis of CRC patients. In addition, SPON2 promotes cytoskeletal remodeling and transendothelial migration of monocytes by activating integrin β1/PYK2 axis. SPON2 may indirectly induce M2-polarization through upregulating cytokines including IL10, CCL2 and CSF1 expression in tumor cells. Blocking M2 polarization and Macrophage depletion inhibited the SPON2-induced tumors growth and invasion. Furthermore, blocking the SPON2/integrin β1/PYK2 axis impairs the transendothelial migration of monocytes and cancer-promoting functions of TAMs in vivo.Our findings demonstrate that SPON2-driven M2-TAM infiltration plays an important role during CRC tumor growth and metastasis. SPON2 may be a valuable biomarker guiding the use of macrophage-targeting strategies and a potential therapeutic target in advanced CRC.© 2021. The Author(s).

基金：
the National Natural Science Foundation of China (No. 81872401).
语种：
外文
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中科院(CAS)分区：
出版当年[2020]版：
大类 | 2 区 医学
小类 | 2 区 肿瘤学
最新[2025]版：
大类 | 1 区 医学
小类 | 1 区 肿瘤学
JCR分区：
出版当年[2019]版：
Q1 ONCOLOGY
最新[2023]版：
Q1 ONCOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2019版] 出版当年五年平均 出版前一年[2018版] 出版后一年[2020版]

第一作者：
第一作者机构： [1]Department of Pathology, Nanfang Hospital, Southern Medical University,Guangzhou 510515, Guangdong, China [2]Department of Pathology, Schoolof Basic Medical Sciences, Southern Medical University, Guangzhou 510515,China [3]Guangdong Provincial Key Laboratory of Molecular Tumor Pathology,Guangzhou, Guangdong, China
共同第一作者：
通讯作者：
通讯机构： [1]Department of Pathology, Nanfang Hospital, Southern Medical University,Guangzhou 510515, Guangdong, China [2]Department of Pathology, Schoolof Basic Medical Sciences, Southern Medical University, Guangzhou 510515,China [3]Guangdong Provincial Key Laboratory of Molecular Tumor Pathology,Guangzhou, Guangdong, China [6]State Key Laboratory of Oncology in South China,Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen UniversityCancer Center, Guangzhou, China
推荐引用方式(GB/T 7714)：
Huang Chengmei,Ou Ruizhang,Chen Xiaoning,et al.Tumor cell-derived SPON2 promotes M2-polarized tumor-associated macrophage infiltration and cancer progression by activating PYK2 in CRC.[J].JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH.2021,40(1):doi:10.1186/s13046-021-02108-0.
APA：
Huang Chengmei,Ou Ruizhang,Chen Xiaoning,Zhang Yaxin,Li Jiexi...&Liao Wenting.(2021).Tumor cell-derived SPON2 promotes M2-polarized tumor-associated macrophage infiltration and cancer progression by activating PYK2 in CRC..JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,40,(1)
MLA：
Huang Chengmei,et al."Tumor cell-derived SPON2 promotes M2-polarized tumor-associated macrophage infiltration and cancer progression by activating PYK2 in CRC.".JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 40..1(2021)

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