Aberrant accumulation of Dickkopf 4 promotes tumor progression via forming the immune suppressive microenvironment in gastrointestinal stromal tumor

Autor: Lin Tu, Xin-Li Ma, Wenyi Zhao, Bo Ni, Ming Wang, Chun Zhuang, Zhigang Zhang, Hui Cao, L X Yang
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Cytotoxicity
Immunologic
Male
Cancer Research
medicine.medical_treatment
Fluorescent Antibody Technique
0302 clinical medicine
Tumor Microenvironment
Stromal tumor
Wnt Signaling Pathway
Original Research
Cancer Biology
GiST
Wnt signaling pathway
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Prognosis
Tumor Burden
Gene Expression Regulation
Neoplastic
Oncology
030220 oncology & carcinogenesis
prognosis indicator
Gene Knockdown Techniques
Disease Progression
Intercellular Signaling Peptides and Proteins
Female
GIST
Gastrointestinal Stromal Tumors
Malignancy
lcsh:RC254-282
03 medical and health sciences
Immune system
Cell Line
Tumor
medicine
Humans
Radiology
Nuclear Medicine and imaging
Aged
Tumor microenvironment
business.industry
Gene Expression Profiling
Immunotherapy
DKK4
medicine.disease
030104 developmental biology
Tumor progression
Cancer research
immune suppression
progression
business
Biomarkers
Zdroj: Cancer Medicine
Cancer Medicine, Vol 8, Iss 11, Pp 5352-5366 (2019)
ISSN: 2045-7634
Popis: Background Drug resistance and tumor recurrence are the major concerns in clinical practices of gastrointestinal stromal tumor (GIST), with the urgent requirement for exploring undiscovered pathways driving malignancy. To deal with these, recent studies have made many efforts to explore prognosis indicators and establish potential therapeutic targets. Methods Expression profiles of different risks of GISTs were described and abundant clinical evidences supported our findings in this study. Following exploration in vitro by cell experiments and verification in vivo using tumor microarray were taken to elucidate the underlying mechanism, which drove the malignancy in GIST. Results Dickkopf 4 (DKK4), as the canonical Wnt pathway antagonist, was unexpectedly and universally upregulated in high‐risk GISTs, and aberrant accumulation of DKK4 was closely correlated with poor prognosis. In addition, tumor‐derived DKK4 could decrease immune cells infiltration and activation in the tumor microenvironment, which decreased the antitumor effects in return. And this phenomenon was recurrent in human tumor specimens. Conclusions Our findings identified DKK4 as a proper tumor biomarker for prognosis predicting and recurrence monitoring, and suggested a novel immune‐escape mechanism driving malignancy in GIST, which might be a potential therapeutic target to improve the effects of canonical RTK therapy and combined immunotherapy.
Databáze: OpenAIRE
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